Interplay and Competition Between Two Different Types of Redox-Active Ligands in Cobalt Complexes: How to Allocate the Electrons?

The field of molecular transition metal complexes with redox-active ligands is dominated by compounds with one or two units of the same redox-active ligand; complexes in which different redox-active ligands are bound to the same metal are uncommon. This work reports the first molecular coordination compounds in which redox-active bisguanidine or urea azine (biguanidine) ligands as well as oxolene ligands are bound to the same cobalt atom. The combination of two different redox-active ligands leads to mono- as well as unprecedented dinuclear cobalt complexes, being multiple (four or six) center redox systems with intriguing electronic structures, all exhibiting radical ligands. By changing the redox potential of the ligands through derivatisation, the electronic structure of the complexes could be altered in a rational way.     

Mechanism and Kinetics for the Reaction of NCS and OH Radicals

The mechanism and dynamical properties for the reaction of NCS and OH radicals have been investigated theoretically. The minimum energy paths (MEP) of the reaction were calculated using the density functional theory(DFT) at the B3LYP/6-311 G^** level, and the energies along the MEP were further refined at the QCISD(T)/6-311 G^** level. As a result, the reaction mechanism of the title reaction involves three channels, producing HCS NO and HNC SO products, respectively. Path Ⅰ and path Ⅱ are competitive, with some advantages for path Ⅰ in kinetics. As for path Ⅲ, it looks difficult to react for its high energy barrier. Moreover, the rate constant have been calculated over the temperature range of 8190-2500K using canonical variational transition-state theory (CVT). It was found that the rate constants for both path Ⅰ and path Ⅱ are negatively dependent on temperature, which is similarwith the experimental results for reactions of NCS with NO and NO2, and the variational effect for the rate constant calculation olavs an important role in whole temperature range.     

The Binding Pocket at the Interface of Multimeric Telomere G-quadruplexes: Myth or Reality?

Human telomeric DNA with hundreds of repeats of the 5’-TTAGGG-3’ motif plays a crucial role in several biological processes. It folds into G-quadruplex (G4) structures and features a pocket at the interface of two contiguous G4 blocks. Up to now no structural NMR and crystallographic data are available for ligands interacting with contiguous G4s. Naphthalene diimide monomers and dyads were investigated as ligands of a dimeric G4 of human telomeric DNA comparing the results with those of the model monomeric G4. Time-resolved fluorescence, circular dichroism, isothermal titration calorimetry and molecular modeling were used to elucidate binding features. Ligand fluorescence lifetime and induced circular dichroism unveiled occupancy of the binding site at the interface. Thermodynamic parameters confirmed the hypothesis as they remarkably change for the dyad complexes of the monomeric and dimeric telomeric G4. The bi-functional ligand structure of the dyads is a fundamental requisite for binding at the G4 interface as only the dyads engage in complexes with 1 : 1 stoichiometry, lodging in the pocket at the interface and establishing multiple interactions with the DNA skeleton. In the absence of NMR and crystallographic data, our study affords important proofs of binding at the interface pocket and clues on the role played by the ligand structure.     

Binding of proteins to the minor groove of DNA: What are the structural and energetic determinants for kinking a basepair step?

The structural and energetic determinants for kinking a basepair step by minor groove-insertion of the protein side chains of PurR, LacI, LEF-1, IHF, Sac7d, and Sso7d, have been calculated by molecular dynamics/potential of mean force simulations. The structural determinants of the kinked structures are: two contiguous furanose rings achieve different conformations, in the region of C3'endo (A-DNA) and C2'endo (B-DNA); the chi torsion angle always takes values characteristic of the C2'endo conformation of B-DNA, independently of sugar puckering; and protein side chain insertion increases slide (from negative to positive values), rise, and roll, and decreases twist. The energetic determinants of DNA kinking are: the conformational transition of the sugar-phosphate backbone is not energetically demanding; the relative importance of the interbase parameters in the free energy penalty is slide, followed by twist and rise, and concluding with shift and roll; and the characteristic increase of roll and decrease of twist, upon side chain insertion, tends to stabilize the process of DNA kinking.     

Highly Modular P?OP Ligands for Asymmetric Hydrogenation: Synthesis,Catalytic Activity,and Mechanism

A library of enantiomerically pure P? OP ligands (phosphine–phosphite), straightforwardly available in two synthetic steps from enantiopure Sharpless epoxy ethers is reported. Both the alkyloxy and phosphite groups can be optimized for maximum enantioselectivity and catalytic activity. Their excellent performance in the Rh‐catalyzed asymmetric hydrogenation of a wide variety of functionalized alkenes (26 examples) and modular design makes them attractive for future applications. The lead catalyst incorporates an (S)‐BINOL‐derived (BINOL=1,1′‐bi‐2‐naphthol) phosphite group with computational studies revealing that this moiety has a dual effect on the behavior of our P? OP ligands. On one hand, the electronic properties of phosphite hinder the binding and reaction of the substrate in two out of the four possible manifolds. On the other hand, the steric effects of the BINOL allow for discrimination between the two remaining manifolds, thereby elucidating the high efficiency of these catalysts.     

Ligand Reprogramming in Dinuclear Helicate Complexes: A Consequence of Allosteric or Electrostatic Effects?

The ditopic ligand 6,6'-bis(4-methylthiazol-2-yl)-3,3'-([18]crown-6)-2,2'-bipyridine (L(1)) contains both a potentially tetradentate pyridyl-thiazole (py-tz) N-donor chain and an additional "external" crown ether binding site which spans the central 2,2'-bipyridine unit. In polar solvents (MeCN, MeNO(2)) this ligand forms complexes with Zn(II), Cd(II), Hg(II) and Cu(I) ions via coordination of the N donors to the metal ion. Reaction with both Hg(II) and Cu(I) ions results in the self-assembly of dinuclear double-stranded helicate complexes. The ligands are partitioned by rotation about the central py--py bond, such that each can coordinate to both metals as a bis-bidentate donor ligand. With Zn(II) ions a single-stranded mononuclear species is formed in which one ligand coordinates the metal ion in a planar tetradentate fashion. Reaction with Cd(II) ions gives rise to an equilibrium between both the dinuclear double-stranded helicate and the mononuclear species. These complexes can further coordinate s-block metal cations via the remote crown ether O-donor domains; a consequence of which are some remarkable changes in the binding modes of the N-donor domains. Reaction of the Hg(II)- or Cd(II)-containing helicate with either Ba(2+) or Sr(2+) ions effectively reprogrammes the ligand to form only the single-stranded heterobinuclear complexes [MM'(L(1))](4+) (M=Hg(II), Cd(II); M'=Ba(2+), Sr(2+)), where the transition and s-block cations reside in the N- and O-donor sites, respectively. In contrast, the same ions have only a minor structural impact on the Zn(II) species, which already exists as a single-stranded mononuclear complex. Similar reactions with the Cd(II) system result in a shift in equilibrium towards the single-stranded species, the extent of which depends on the size and charge of the s-block cation in question. Reaction of the dicopper(I) double-stranded helicate with Ba(2+) shows that the dinuclear structure still remains intact but the pitch length is significantly increased.     

Mechanism of HCS + O2 reaction: hydrogen- or oxygen-transfer?

In spite of the potential importance of the HCS radical in both combustion and interstellar processes, its chemical reactivity has not been tackled previously. In the present paper, the oxidation reaction of the HCS radical is theoretically investigated for the first time at the CCSD(T)/6-311++G(3df,2p)//BH&HLYP/6-311++G(d,p)+ZPVE and Gaussian-3//B3LYP/6-31G(d) levels. It is shown that the most feasible pathway is the O2 addition to the HCS radical forming the intermediate SC(H)OO which can undergo a subsequent O-extrusion leading to SC(H)O + 3O. This features an indirect O-transfer mechanism with the overall barrier of 4.4 and 3.5 kcal mol(-1), respectively, at the two levels. However, formation of the H-transfer product CS + HO2 is kinetically much less feasible, i.e., the direct mechanism has barriers of 14.3 and 8.7 kcal mol(-1), whereas the indirect mechanism has barriers of 12.6 and 10.7 kcal mol(-1), respectively. This result is in sharp contrast to the analogous HCO + O2 reaction, where the direct (with a barrier of 2.98 kcal mol(-1)) and indirect (2.26 kcal mol(-1)) H-transfer processes are highly competitive over the indirect O-transfer process (the least endothermicity is 19.9 kcal mol(-1)). The possible explanations and implications of the present results are provided.     

De Novo Design of Selective Quadruplex–Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot

Targeting the interface between DNA quadruplex and duplex regions by small molecules holds significant promise in both therapeutics and nanotechnology. Herein, a new pharmacophore is reported, which selectively binds with high affinity to quadruplex–duplex junctions, while presenting a poorer affinity for G-quadruplex or duplex DNA alone. Ligands complying with the reported pharmacophore exhibit a significant affinity and selectivity for quadruplex–duplex junctions, including the one observed in the HIV-1 LTR-III sequence. The structure of the complex between a quadruplex–duplex junction with a ligand of this family has been determined by NMR methods. According to these data, the remarkable selectivity of this structural motif for quadruplex–duplex junctions is achieved through an unprecedented interaction mode so far unexploited in medicinal and biological chemistry: the insertion of a benzylic ammonium moiety into the centre of the partially exposed G-tetrad at the interface with the duplex. Further decoration of the described scaffolds with additional fragments opens up the road to the development of selective ligands for G-quadruplex-forming regions of the genome.     

Mechanism and controlling strategy of the production and accumulation of propionic acid for anaerobic wastewater treatment

The production and accumulation of propionic acid affect significantly anaerobic wastewater treatment system, but the reasons are not approached until now. Based on the results of continuous-flow tests and the analysis of biochemistry and ecology, two mechanisms of producing propionic acid have been put forward. It is demonstrated that the reasons of propionic acid production and accumulation are not caused by higher hydrogen partial pressure. The combination of specific pH value and ORP is the ecological factor affecting propionic acid production, and the equilibrium regulation of NADH/NAD+ ratio in cells is the physiological factor. Meanwhile, it is put forward that using the two-phase anaerobic treatment process and the ethanol type fermentation in anaerobic reactor to avoid propionic acid accumulation are efficient methods.     

Selection of Peptide Ligands Specific for Baculovirus DNA‐Binding Protein from the Flitrx™ Random Peptide Display Library

Abstract

Autographa californica nucleopolyhedrovirus (AcNPV) is a baculovirus that is widely employed as a vector for the expression of foreign genes and pest control. Although baculoviruses, including AcNPV, efficiently replicate in the nuclei of arthropod cells, the dynamics and mechanism of DNA replication within the infected cell are still poorly understood. It has been found that the DNA‐binding protein (DBP) is an early gene product and appears to be crucial for viral DNA replication.

Presented here is the selection of peptide ligands that specifically bind to DBP for AcNPV from the FliTrx? random peptide display library; this entails the amplification, cloning of the DNA‐binding protein (DBP) gene from AcNPV and the construction of the expression plasmid for DBP, and the expression and purification of the recombinant His.Tag AcNPV DBP that was used as a target molecule for the selection of the peptide ligands specific for AcNPV DBP. The affinity and efficiency of such peptide ligands were then measured by ELISA procedures.

The beneficial aspect of this research is the monospecificity quality of the peptide ligands specific for AcNPV DBP. They could be used for the study of the dynamics of the viral genome and its replication within the infected cell, for the development of a quantitative method for the determination of the presence of baculovirus in various samples, for the development of a peptide ligandbased assay for the determination of baculovirus titers; or they could be immobilized on a chromatographic support for an improved affinity purification of AcNPV DBP.     

Mechanism of GTP: Can all of the available data be accommodated?

Group transfer polymerization (GTP)^a of acrylic monomers is a living system mediated by a trialkylsilyl capped growing chain end. The fact that it operates at temperatures as high as 100° C differentiates GTP from living anionic polymerization, which at best operates at 25° C for hindered methacrylates. To accommodate all of the mechanistic data available it appears that at least two mechanistic pathways are required: an associative process for mild nucleophilic catalysts and a dissociative process for strong nucleophilic catalysts.     

Mechanism of Mukaiyama-Michael Reaction of Ketene Silyl Acetal: Electron Transfer or Nucleophilic Addition?

Mechanism of Mukaiyama-Michael reaction of ketene silyl acetal has been discussed. The competition reaction employing various types of ketene silyl acetals reveals that those bearing more substituents at the beta-position react preferentially over less substituted ones. However, when ketene silyl acetals involve bulky siloxy and/or alkoxy group(s), less substituted compounds react preferentially. The Lewis acids play an important role in these reactions. Enhanced preference for the more sterically demanding Michael adducts is obtained with Bu(2)Sn(OTf)(2), SnCl(4), and Et(3)SiClO(4) in the former reaction while TiCl(4) gives the highest selectivity for the less sterically demanding products in the latter case. These results are interpreted in terms of alternative reaction mechanisms. The reaction of less bulky ketene silyl acetals are initiated by electron transfer from these compounds to a Lewis acid. On the other hand, bulkier ketene silyl acetals undergo a ubiquitous nucleophilic reaction. Such a mechanistic change is discussed based on a variety of experimental results as well as the semiempirical PM3 MO calculations.     

Competition between receptors in dynamic combinatorial libraries: amplification of the fittest?

Dynamic combinatorial chemistry is a powerful tool for the discovery of strong binders (synthetic receptors or ligands) because binding causes a shift in the equilibrium of library members toward those that bind well. Ideally, the best binders are selectively amplified. However, theoretical studies predict this is not always the case. This paper describes the first quantitative experimental evidence proving that, under special circumstances, the preferential amplification of suboptimal synthetic receptors can indeed occur. Our results also demonstrate that reducing the amount of guest in the library can rectify such undesirable behavior and ensures selective amplification of the fittest receptor.     

Chemo-enzymatic Synthesis and RAFT Polymerization of 6-O-Methacryloyl Mannose: A Suitable Glycopolymer for Binding to the Tetrameric Lectin Concanavalin A?

Summary: The chemo-enzymatic synthesis of 6-O-methacryloyl mannose (MaM) glycomonomer was successfully performed for the first time. Subsequent aqueous RAFT polymerization of the monomer yielded well-defined, linear poly(6-O-methacryloyl mannose) (PMaM) glycopolymers without the need for protecting and deprotecting group chemistry. As well as investigating the RAFT polymerization kinetics of this monomer using various initial monomer to chain transfer agent concentration ratios, the protein binding ability of the generated glycopolymer was tested using concanavalin A, a known mannose-residue binding lectin.     

Investigation of the mechanisms of the action of chemical modifiers for electrothermal atomic absorption spectrometry: what for and how?

Modern trends in the research of the action of chemical modifiers for electrothermal atomic absorption spectrometry (ETAAS) are discussed critically. The most prolific approach is that of investigation of processes occurring during the drying and pyrolysis stages with wide application of data from different fields of chemistry and physics.     

Investigation of the Mitsunobu Reaction of BINOL and Cinchona Alkaloids: Inversion or Retention of Configuration?

An efficient approach toward the construction of multistereogenic binaphthol (BINOL)–derived alkaloids with C₂-axial and sp³ central chirality has been accomplished. The reaction of BINOL and cinchona alkaloids was occurred smoothly under the Mitsunobu conditions, which led to the synthesis of a new family of complicated functional molecules based on chiral BINOL and cinchona alkaloids. In addition, on the basis of the experimental results, we provided a possible explanation for the intramolecular tertiary amine-induced retention of configuration at C9 of cinchona alkaloids while the inversion of configuration was observed with general alcohols under classic Mitsunobu conditions.