An enzymatic kinetics investigation into the significantly enhanced activity of functionalized gold nanoparticles

Kinetic and thermodynamic studies reveal that the property of significantly enhanced catalytic activity with colloidal stability is attributed to an efficacious means of tuning enzyme-substrate association by varying with the rate constants in the presence of functionalized gold nanoparticles.     

寡糖合成中的“预活化”策略

寡糖及其缀合物因其重要的生物学功能而日益受到人们的关注,由于糖链结构的复杂性与多样性,寡糖的化学合成具有很大的挑战性。为了减少合成及分离步骤,提高寡糖合成的效率,糖基化策略十分重要。"一釜合成法"由于进行多个连续的糖基化反应但不需分离中间体而具有很大优势,但传统"一釜法"在设计单糖模块时需要进行精细复杂的保护基操作和离去基调整而影响其合成效率。"预活化"寡糖合成策略不依赖于糖基供体与糖基受体的活性差异,无需复杂的保护基操作,所有偶联反应在同一条件下一釜完成,实现了寡糖的高效、快速合成。本文在简要介绍传统"一釜合成法"的基础上,对"预活化"策略的研究进展进行综述,重点介绍"预活化"策略的基本原理,发展过程及其在生物活性寡糖合成上的应用。     

Complexation chemistry for tuning release from polymer coatings

The strategy of metal ion complexation is employed to design a delivery system for an antifouling agent (AFA) in marine paints. A poly(1-vinylimidazole-co-methyl methacrylate) copolymer (PVM), together with Cu2+ or Zn2+ formed a PVM-M2+ complex. The AFA, Medetomidine, was then coordinated into the complex. The coordination strength was investigated in solution by 1H NMR and on solid surfaces by using the Quartz Crystal Microbalance with Dissipation monitoring technique (QCM-D) and Surface Plasmon Resonance (SPR). From the 1H NMR experiments strong interactions were observed between Cu2+ and the PVM-polymer and between Medetomidine and the PVM-Cu2+ complex. From the QCM-D and SPR measurements it was shown that Cu2+, compared to Zn2+, exhibited a larger affinity for the PVM-copolymer surface that resulted in higher degree of swelling of the polymer film. Large amounts of Medetomidine were adsorbed to the PVM-Cu2+ complex resulting in low desorption rates. However, the adsorbed amount of Medetomidine was lower to the Zn2+ doped polymer and a higher desorption rate was observed. These results indicate the possibility of tuning the release of Medetomidine by altering the coordinating metal ion, which may prove to be favorable in a paint formulation.     

Hetero-assembly of gold nanoparticles on a DNA origami template

Hetero-assembling of spherical building blocks with well-defined spatial distribution holds great significance in developing chiral nanostructures. Herein, a strategy for hetero-assembling of gold nanoparticles(Au NPs) was demonstrated using rigid bifacial DNA origami as templates. By tuning the sizes and the fixed location of Au NPs on DNA origami, right-handed and left-handed Au NPs nanostructures were respectively constructed. Gel electrophoresis indicated the formation of the DNA origami-Au NPs complex and transmission electron microscopy(TEM) visually displayed the arrangement of Au NPs in these two chiral structures. The spatial configuration and 3D geometry of Au NPs were further illustrated by the stereographic TEM with tilting angles from ?30° to 30°. This strategy provides a universal approach to construct the asymmetrical 3D geometries, which may have potential applications in biomimicking and nanophotonics.     

Understanding and tuning the catalytic bias of hydrogenase

When enzymes are optimized for biotechnological purposes, the goal often is to increase stability or catalytic efficiency. However, many enzymes reversibly convert their substrate and product, and if one is interested in catalysis in only one direction, it may be necessary to prevent the reverse reaction. In other cases, reversibility may be advantageous because only an enzyme that can operate in both directions can turnover at a high rate even under conditions of low thermodynamic driving force. Therefore, understanding the basic mechanisms of reversibility in complex enzymes should help the rational engineering of these proteins. Here, we focus on NiFe hydrogenase, an enzyme that catalyzes H(2) oxidation and production, and we elucidate the mechanism that governs the catalytic bias (the ratio of maximal rates in the two directions). Unexpectedly, we found that this bias is not mainly determined by redox properties of the active site, but rather by steps which occur on sites of the proteins that are remote from the active site. We evidence a novel strategy for tuning the catalytic bias of an oxidoreductase, which consists in modulating the rate of a step that is limiting only in one direction of the reaction, without modifying the properties of the active site.     

Effective manipulation of the electronic effects and its influence on the emission of 5-substituted tris(8-quinolinolate) aluminum(III) complexes

The unique electron-transport and emissive properties of tris(8-quinolinolate) aluminum(III) (Alq(3)) have resulted in extensive use of this material for small molecular organic light-emitting diode (OLED) fabrication. So far, efforts to prepare stable and easy-to-process red/green/blue (RGB)-emitting Alq(3) derivatives have met with only a limited success. In this paper, we describe how the electronic nature of various substituents, projected via an arylethynyl or aryl spacer to the position of the highest HOMO density (C5), may be used for effective emission tuning to obtain blue-, green-, and red-emitting materials. The synthetic strategy consists of four different pathways for the attachment of electron-donating and electron-withdrawing aryl or arylethynyl substituents to the 5-position of the quinolinolate ring. Successful tuning of the emission color covering the whole visible spectrum (lambda=450-800 nm) was achieved. In addition, the photophysical properties of the luminophores were found to correlate with the Hammett constant of the respective substituents, providing a powerful strategy with which to predict the optical properties of new materials. We also demonstrate that the electronic nature of the substituent affects the emission properties of the resulting complex through effective modification of the HOMO levels of the quinolinolate ligand.     

Design of Complex Solid‐Solution Electrocatalysts by Correlating Configuration,Adsorption Energy Distribution Patterns,and Activity Curves

Complex solid‐solution electrocatalysts (also referred to as high‐entropy alloy) are gaining increasing interest owing to their promising properties which were only recently discovered. With the capability of forming complex single‐phase solid solutions from five or more constituents, they offer unique capabilities of fine‐tuning adsorption energies. However, the elemental complexity within the crystal structure and its effect on electrocatalytic properties is poorly understood. We discuss how addition or replacement of elements affect the adsorption energy distribution pattern and how this impacts the shape and activity of catalytic response curves. We highlight the implications of these conceptual findings on improved screening of new catalyst configurations and illustrate this strategy based on the discovery and experimental evaluation of several highly active complex solid solution nanoparticle catalysts for the oxygen reduction reaction in alkaline media.     

Unraveling solvent-driven equilibria between alpha- and 3(10)-helices through an integrated spin labeling and computational approach

In this work we present an effective and flexible computational approach, which is the result of an ongoing development in our groups, allowing the complete a priori simulation of the ESR spectra of complex systems in solution. The usefulness and reliability of the method are demonstrated on the very demanding playground represented by the tuning of the equilibrium between 3(10)- and alpha-helices of polypeptides by different solvents. The starting point is the good agreement between computed and X-ray diffraction structures for the 3(10)-helix adopted by the double spin-labelled heptapeptide Fmoc-(Aib-Aib-TOAC)2-Aib-OMe. Next, density functional computations, including dispersion interactions and bulk solvent effects, suggest another energy minimum corresponding to an alpha-helix in polar solvents, which, eventually, becomes the most stable structure. Computation of magnetic and diffusion tensors provides the basic ingredients for the building of complete spectra by methods rooted in the Stochastic Liouville Equation (SLE). The remarkable agreement between computed and experimental spectra at different temperatures allowed us to identify helical structures in the various solvents. The generality of the computational strategy and its implementation in effective and user-friendly computer codes pave the route toward systematic applications in the field of biomolecules and other complex systems.     

How Sensitive is the Amide I Vibration of the Polypeptide Backbone to Electric Fields?

Site‐selective isotopic labeling of amide carbonyls offers a nonperturbative means to introduce a localized infrared probe into proteins. Although this strategy has been widely used to investigate various biological questions, the dependence of the underlying amide I vibrational frequency on electric fields (or Stark tuning rate) has not been fully determined, which prevents it from being used in a quantitative manner in certain applications. Herein, through the use of experiments and molecular dynamics simulations, the Stark tuning rate of the amide I vibration of an isotopically labeled backbone carbonyl in a transmembrane α‐helix is determined to be approximately 1.4 cm^?1/(MV/cm). This result provides a quantitative basis for using this vibrational model to assess local electric fields in proteins, among other applications. For instance, by using this value, we are able to show that the backbone region of a dipeptide has a surprisingly low dielectric constant.     

Stacked but not Stuck: Unveiling the Role of π→π* Interactions with the Help of the Benzofuran–Formaldehyde Complex

The 1:1 benzofuran–formaldehyde complex has been chosen as model system for analyzing π→π* interactions in supramolecular organizations involving heteroaromatic rings and carbonyl groups. A joint “rotational spectroscopy–quantum chemistry” strategy unveiled the dominant role of π→π* interactions in tuning the intermolecular interactions of such adduct. The exploration of the intermolecular potential energy surface led to the identification of 14 low-energy minima, with 4 stacked isomers being more stable than those linked by hydrogen bond or lone-pair→π interactions. All energy minima are separated by loose transition states, thus suggesting an effective relaxation to the global minimum under the experimental conditions. This expectation has been confirmed by the experimental detection of only one species, which was unambiguously assigned owing to the computation of accurate spectroscopic parameters and the characterization of 11 isotopologues. The large number of isotopic species opened the way to the determination of the first semi-experimental equilibrium structure for a molecular complex of such a dimension.     

Highly luminescent mixed-metal Pt(II)/Ir(III) complexes: bis-cyclometalation of 4,6-diphenylpyrimidine as a versatile route to rigid multimetallic assemblies

The proligand 4,6-di-(4-tert-butylphenyl)pyrimidine LH(2) can undergo cycloplatination with K(2)PtCl(4) at one of the two aryl rings to give, after treatment with sodium acetylacetonate, a mononuclear complex Pt(N^C-LH)(acac) (denoted Pt). If an excess of K(2)PtCl(4) is used, a dinuclear complex of the form [Pt(acac)](2){μ-(N^C-L-N^C)} (Pt(2)) is obtained instead, where the pyrimidine ring acts as a bridging unit. Alternatively, the mononuclear complex can undergo cyclometalation with a different metal ion. Thus, reaction of Pt with IrCl(3)·3H(2)O (2:1 ratio) leads, after treatment with sodium acetylacetonate, to an unprecedented mixed-metal complex of the form Ir{μ-(N^C-L-N^C)Pt(acac)}(2)(acac) (Pt(2)Ir). The mononuclear iridium complex Ir(N^C-LH)(2)(acac) (Ir) has also been prepared for comparison. The UV-visible absorption and photoluminesence properties of the four complexes and of the proligand have been investigated. The complexes are all highly luminescent, with quantum yields of around 0.5 in solution at room temperature. The introduction of the additional metal centers is found to lead to a substantial red-shift in absorption and emission, with λ(max) in the order Pt < Pt(2) < Ir < Pt(2)Ir. The trend is interpreted with the aid of electrochemical data and density functional theory calculations, which suggest that the red-shift is due primarily to a progressive stabilization of the lowest unoccupied molecular orbital (LUMO). The radiative decay constant is also increased. This versatile design strategy may offer a new approach for tuning and optimizing the luminescence properties of d-block metal complexes for contemporary applications.     

Switching the emission of di(4-ethoxyphenyl)dibenzofulvene among multiple colors in the solid state

Luminescent materials exhibiting emission switching in the solid state have drawn much attention though there is still no clear design strategy for such materials. In this letter, we reported the crystallization induced emission enhancement (CIEE) of di(4-ethoxyphenyl)dibenzofulvene (1), and achieved switching its emission among four different colors through modulation of its molecular packing patterns. We have investigated its potential application as optical recording materials. The twisted conformations of CIEE compounds afford morphology dependent emission and facilitate tuning their emission through modulation of molecular packing patterns. Thus we provide a possible design strategy for solid stimulus responsive luminescent materials.     

Selectivity optimization in liquid chromatography via stationary phase tuning

In striving for the best possible separation, the selectivity of stationary phases as an optimization parameter is often underestimated although there are many ways to influence this powerful tool. This review serves to provide an insight into the various ways of adapting the selectivity of a separation in liquid chromatography. Approaches via temperature and flow rate tuning are discussed as a basis followed by focusing on the stationary phase as the superior optimization parameter. Highly selective stationary phases hereby provide an advantage for groups of similar analytes. For more complex mixtures, separations can be improved using mixed-mode technologies where different retention mechanisms are combined. Serial coupling, mixed-bed columns, and stationary phase optimized selectivity liquid chromatography provide solutions to various degrees. Finally, the advantages of stationary phase tuning over adaption of mobile phase and/or temperature are presented in terms of optimum application range.     

Xanthine Oxidase Inhibitors from Filipendula ulmaria (L.) Maxim. and Their Efficient Detections by HPTLC and HPLC Analyses

Filipendula ulmaria is a plant commonly used for the treatment of several pathologies, such as diarrhoea, ulcers, pain, stomach aches, fevers, and gout. Our study focused on the use of F. ulmaria for the treatment of gout disease. We first studied the chemical composition of a methanolic extract of the aerial parts and demonstrated its xanthine oxidase (XO) inhibitory activity. Then, we performed a fractionation and evaluated the most XO inhibitory active fractions by UV measurement. Purification of some fractions allowed the determination of the inhibitory activity of pure compounds. We demonstrated that spiraeoside, a glycosylated flavonoid, possesses an activity around 25 times higher than allopurinol, used as a reference in the treatment of gout disease. In order to easily and quickly identify potent inhibitors in complex matrix, we developed a complementary strategy based on an HPLC method and an Effect Directed Assay (EDA) method combining HPTLC and biochemical assays. The HPLC method, capable of determining compounds exhibiting interactions with the enzyme, could be an efficient strategy for evaluating potent enzyme inhibitors in a complex mixture. This strategy could be applied for quantitative assays using LC/MS experiments.     

Selective Extraction of Metal Ions from Aqueous Phase to Ionic Liquids: A Novel Thermodynamic Approach to Separations

The selective extraction of metals from aqueous mixtures has generally relied on the use of selective ionophores. We present an alternative strategy that exploits a recently developed approach to extraction into an ionic liquid phase, and show that a high degree of control over selectivity can be obtained by tuning the relative concentrations of extraction agents. A thermodynamic model for the approach is presented, and an experimental separation of strontium and potassium ions is performed. It is shown that tuning the concentrations of the species involved can shift the ratio of potassium to strontium in the ionic liquid phase from 4:1 to 3:4. This extraction is performed under mild conditions with relatively common reagents. The result is a proof‐of‐concept for a novel separations scheme that could have great importance in a wide range of technological applications.     

Affinity capillary electrophoresis of DNA for detection of single-nucleotide polymorphisms and point mutations. Comprehensive study for optimization of the weak affinity

A single-stranded DNA and its point mutant can be separated with affinity capillary electrophoresis (ACE) in which an appropriate ligand DNA is used as a pseudo-stationary affinity phase. In this paper, we systematically examine the effects of ligand sequence, capillary temperature, and cation concentration on the ACE separation quality, which is quantitatively evaluated in terms of resolution and peak height. For fine tuning of the affinity, control of MgCl(2) concentration and insertion of a spacer sequence into the ligand DNA are more effective than control of the capillary temperature. For design of the ligand DNA, a simple strategy is proposed, based on the prediction of melting temperature. This strategy was tested with eleven different sample sequences. All of them were separated under the same conditions (250 microM MgCl(2) and 25 degrees C), and nine cases of them had satisfactory separation qualities.     

Catalytic asymmetric Michael reaction of beta-keto esters: effects of the linker heteroatom in linked-BINOL

We describe the development of a general catalytic asymmetric Michael reaction of acyclic beta-keto esters to cyclic enones, in which asymmetric induction occurs at the beta-position of the acceptors. Among the various asymmetric catalyst systems examined, the newly developed La-NR-linked-BINOL complexes (R = H or Me) afforded the best results in terms of reactivity and selectivity. In general, the NMe ligand 2 was suitable for the combination of small enones and small beta-keto esters, and the NH ligand 1 was suitable for bulkier substrates (steric tuning of the catalyst). Using the La-NMe-linked-BINOL complex, the Michael reaction of methyl acetoacetate (8a) to 2-cyclohexen-1-one (7b) gave the corresponding Michael adduct 9ba in 82% yield and 92% ee. The linker heteroatom in linked-BINOL is crucial for achieving high reactivity and selectivity in the Michael reaction of beta-keto esters. The amine moiety in the NR-linked-BINOL can also tune the Lewis acidity of the central metal (electronic tuning of the catalyst), which was supported by density functional studies and experimental results. Another advantage of the NR-linked-BINOL ligand as compared with O-linked-BINOL is the ease of modifying a substituent on the amine moiety, making it possible to synthesize a variety of NR-linked-BINOL ligands for further improvement or development of new asymmetric catalyses by introducing additional functionality on the linker with the amine moiety. The efficiency of the present asymmetric catalysis was demonstrated by the synthesis of the key intermediate of (-)-tubifolidine and (-)-19,20-dihydroakuammicine in only five steps compared to the nine steps required by the original process from the Michael product of malonate. This strategy is much more atom economical. On the basis of the results of mechanistic studies, we propose that a beta-keto ester serves as a ligand as well as a substrate and at least one beta-keto ester should be included in the active catalyst complex. Further improvement of the reaction by maintaining an appropriate ratio of the La-NMe-linked-BINOL complex and beta-keto esters is also described.     

Surface plasmon resonance study of the interaction of a beta-cyclodextrin polymer and hydrophobically modified poly(N-isopropylacrylamide)

Surface plasmon resonance (SPR) technique is used to follow, both in real time and in situ, the association between a physically adsorbed polymer of beta-cyclodextrin (pbetaCD) and different hydrophobically modified poly(N-isopropylacrylamide) (PNIPAM) copolymers containing either adamantyl or dodecyl groups. This association is due to the complex formation between the hydrophobic groups and the betaCD cavities. Therefore, the adsorbed amount of PNIPAM onto the pbetaCD layer depends on the substituent and on its substitution level. The association and dissociation rate constants are evaluated from the kinetics of PNIPAM adsorption. An estimation of the association constants leads to values higher than 10(4) M(-1), reflecting the strong interaction between these polymers.     

Enhancement of Antiangiogenic Efficacy of Iron(II) Complex by Selenium Substitution

Antiangiogenesis therapy is a proven strategy for the treatment of cancers. Herein, we demonstrate that iron(II) complexes containing 1,10‐phenanthroline(phen) derivatives were capable of suppressing angiogenesis in vitro in a dose‐dependent manner. Interestingly, the introduction of selenium into an iron(II) complex ((Fe(phenSe)₃(ClO₄)₂ (phenSe=2‐selenoimidazole[4,5‐f]1,10‐phenanthroline)) could enhance its antiangiogenic efficacy. Mechanistic studies demonstrated that the complex potently induced endothelial cell apoptosis as evidenced by activation of caspases and PARP cleavage. The iron(II) complex activated p53‐mediated mitochondrial dysfunction as can be seen by the upregulation in the expression of p53 and proapoptotic Bcl‐2 family proteins, and downregulation in the expression of Bcl‐2 family proteins. Additionally, the complex inhibited VEGF expression and gave rise to dephosphorylated AKT, which suppressed the transmission of the mitogenic signaling pathway. Taken together, this study could provide a strategy for the rational design of high‐efficacy antivascular agents.     

Achieving flexible large-scale reactivity tuning by controlling the phase,thickness and support of two-dimensional ZnO

Tuning surface reactivity of catalysts is an effective strategy to enhance catalytic activity towards a chemical reaction. Traditional reactivity tuning usually relies on a change of the catalyst composition, especially when large-scale tuning is desired. Here, based on density functional theory calculations, we provide a strategy for flexible large-scale tuning of surface reactivity, i.e. from a few tenths of electronvolts (eV) to multiple eV, merely through manipulating the phase, thickness, and support of two-dimensional (2D) ZnO films. 2D ZnO films have three typical phases, i.e. graphene, wurtzite, and body-centered-tetragonal structures, whose intrinsic stability strongly depends on the thickness and/or the chemical nature of the support. We show that the adsorption energy of hydrogen differs by up to 3 eV on these three phases. For the same phase, varying the film thickness and/or support can lead to a few tenths of eV to 2 eV tuning of surface reactivity. We further demonstrate that flexible large-scale tuning of surface reactivity has a profound impact on the reaction kinetics, including breaking the Brønsted–Evans–Polanyi relationship.

Flexible large-scale reactivity tuning is achieved by manipulating the phase, thickness and support of two-dimensional ZnO, and a broken scaling relationship between adsorption and barrier is found via phase and termination engineering.