Dynamic covalent chemistry on surfaces employing highly reactive cyclopentadienyl moieties

Silicon substrates coated with a bromide-terminated silane are transformed into highly reactive, cyclopentadiene covered analogues. These surfaces undergo rapid cycloaddition reactions with various dienophile-capped polymers. Mild heating of the substrates causes the retro-Diels-Alder reaction to occur, thus reforming the reactive cyclopentadiene surface, generating an efficiently switchable surface.

Photoclickable surfaces for profluorescent covalent polymer coatings

The nitrile imine-mediated tetrazole-ene cycloaddition reaction (NITEC) is introduced as a powerful and versatile conjugation tool to covalently ligate macromolecules onto variable (bio)surfaces. The NITEC approach is initiated by UV irradiation and proceeds rapidly at ambient temperature yielding a highly fluorescent linkage. Initially, the formation of block copolymers by the NITEC methodology is studied to evidence its efficacy as a macromolecular conjugation tool. The grafting of polymers onto inorganic (silicon) and bioorganic (cellulose) surfaces is subsequently carried out employing the optimized reaction conditions obtained from the macromolecular ligation experiments and evidenced by surface characterization techniques, including X-ray photoelectron spectroscopy and FT-IR microscopy. In addition, the patterned immobilization of variable polymer chains onto profluorescent cellulose is achieved through a simple masking process during the irradiation. Photoinduced nitrile imine-alkene 1,3-dipolar cycloaddition (NITEC) is employed to covalently bind well-defined polymers onto silicon oxide or cellulose. A diaryl tetrazole-functionalized molecule is grafted via silanization or amidification, respectively. Under UV light, a reactive nitrile imine rapidly forms and reacts with maleimide-functionalized polymers yielding a fluorescent linkage. Via a masking method, polymeric fluorescent patterns are achieved.

Non-covalent surface modification of boron nitride nanotubes for enhanced catalysis

Boron nitride nanotubes were functionalized by microperoxidase-11 in aqueous media, showing improved catalytic performance due to a strong electron coupling 10 between the active centre of microperoxidase-11 and boron nitride nanotubes. One main application challenge of enzymes as biocatalysts is molecular aggregation in the aqueous solution. This issue is addressed by immobilization of enzymes on solid supports which 15 can enhance enzyme stability and facilitate separation, and recovery for reuse while maintaining catalytic activity and selectivity. The protein-nanoparticle interactions play a key role in bio-nanotechnology and emerge with the development of nanoparticle-protein “corona”. Bio-molecular coronas provide a 20 unique biological identity of nanosized materials.1, 2 As a structural analogue to carbon nanotubes (CNTs), Boron nitride nanotubes have boron and nitrogen atoms distributed equally in hexagonal rings and exhibit excellent mechanical strength, unique physical properties, and chemical stability at high-temperatures. 25 The chemical inertness of BN materials suits to work in hazardous environments, making them an optimal candidate in practical applications in biological and medical field.3, 4

Tunable electric field enhancement and redox chemistry on TiO2 island films via covalent attachment to Ag or Au nanostructures

Abstract Ag-TiO2 and Au-TiO2 hybrid electrodes were designed by covalent attachment of TiO2 nanoparticles to Ag or Au electrodes via an organic linker. The optical and electronic properties of these systems were investigated using the cytochrome b5 (Cyt b5) domain of sulfite oxidase, exclusively attached to the TiO2 surface, as a Raman marker and model redox enzyme. Very strong SERR signals of Cyt b 5 were obtained for Ag-supported systems due to plasmonic field enhancement of Ag. Time-resolved surface-enhanced resonance Raman spectroscopic measurements yielded a remarkably fast electron transfer kinetic (k = 60 s -1) of Cyt b5 to Ag. A much lower Raman intensity was observed for Au-supported systems with undefined and slow redox behavior. We explain this phenomenon on the basis of the different potential of zero charge of the two metals that largely influence the electronic properties of the TiO2 island film. © 2013 American Chemical Society.

Effect of covalent functionalisation on thermal transport across graphene-polymer interfaces

This paper is concerned with the interfacial thermal resistance for polymer composites reinforced by various covalently functionalised graphene. By using molecular dynamics simulations, the obtained results show that the covalent functionalisation in graphene plays a significant role in reducing the graphene-paraffin interfacial thermal resistance. This reduction is dependent on the coverage and type of functional groups. Among the various functional groups, butyl is found to be the most effective in reducing the interfacial thermal resistance, followed by methyl, phenyl and formyl. The other functional groups under consideration such as carboxyl, hydroxyl and amines are found to produce negligible reduction in the interfacial thermal resistance. For multilayer graphene with a layer number up to four, the interfacial thermal resistance is insensitive to the layer number. The effects of the different functional groups and the layer number on the interfacial thermal resistance are also elaborated using the vibrational density of states of the graphene and the paraffin matrix. The present findings provide useful guidelines in the application of functionalised graphene for practical thermal management.

Polymer nanocomposites based on P3OT, TPU and SWNT: preparation and characterization

Single walled carbon nanotubes (SWNTs) were incorporated in polymer nanocomposites based on poly(3-octylthiophene) (P3OT), thermoplastic polyurethane (TPU) or a blend of them. Thermogravimetry demonstrated the success of the purification procedure employed in the chemical treatment of SWNTs prior to composite preparation. Stable dispersions of SWNTs in chloroform were obtained by non-covalent interactions with the dissolved polymers. Composites exhibited glass transitions, melting temperatures and heat of fusion which changed in relation to pure polymers. This behavior is discussed as associated to interactions between nanotubes and polymers. The conductivity at room temperature of the blend (TPU-P3OT) with SWNT is higher than the P3OT/SWNT composite.

A surface plasmon resonance-based solution affinity assay for heparan sulfate-binding proteins

A surface plasmon resonance-based solution affinity assay is described for measuring the Kd of binding of heparin/heparan sulfate-binding proteins with a variety of ligands. The assay involves the passage of a pre-equilibrated solution of protein and ligand over a sensor chip onto which heparin has been immobilised. Heparin sensor chips prepared by four different methods, including biotin–streptavidin affinity capture and direct covalent attachment to the chip surface, were successfully used in the assay and gave similar Kd values. The assay is applicable to a wide variety of heparin/HS-binding proteins of diverse structure and function (e.g., FGF-1, FGF-2, VEGF, IL-8, MCP-2, ATIII, PF4) and to ligands of varying molecular weight and degree of sulfation (e.g., heparin, PI-88, sucrose octasulfate, naphthalene trisulfonate) and is thus well suited for the rapid screening of ligands in drug discovery applications.

Dynamics of transformation and fragmentation of composite liquid nano-particles

Recent research on particle size distributions and particle concentrations near a busy road cannot be explained by the conventional mechanisms for particle evolution of combustion aerosols. Specifically they appear to be inadequate to explain the experimental observations of particle transformation and the evolution of the total number concentration. This resulted in the development of a new mechanism based on their thermal fragmentation, for the evolution of combustion aerosol nano-particles. A complex and comprehensive pattern of evolution of combustion aerosols, involving particle fragmentation, was then proposed and justified. In that model it was suggested that thermal fragmentation occurs in aggregates of primary particles each of which contains a solid graphite/carbon core surrounded by volatile molecules bonded to the core by strong covalent bonds. Due to the presence of strong covalent bonds between the core and the volatile (frill) molecules, such primary composite particles can be regarded as solid, despite the presence of significant (possibly, dominant) volatile component. Fragmentation occurs when weak van der Waals forces between such primary particles are overcome by their thermal (Brownian) motion. In this work, the accepted concept of thermal fragmentation is advanced to determine whether fragmentation is likely in liquid composite nano-particles. It has been demonstrated that at least at some stages of evolution, combustion aerosols contain a large number of composite liquid particles containing presumably several components such as water, oil, volatile compounds, and minerals. It is possible that such composite liquid particles may also experience thermal fragmentation and thus contribute to, for example, the evolution of the total number concentration as a function of distance from the source. Therefore, the aim of this project is to examine theoretically the possibility of thermal fragmentation of composite liquid nano-particles consisting of immiscible liquid v components. The specific focus is on ternary systems which include two immiscible liquid droplets surrounded by another medium (e.g., air). The analysis shows that three different structures are possible, the complete encapsulation of one liquid by the other, partial encapsulation of the two liquids in a composite particle, and the two droplets separated from each other. The probability of thermal fragmentation of two coagulated liquid droplets is discussed and examined for different volumes of the immiscible fluids in a composite liquid particle and their surface and interfacial tensions through the determination of the Gibbs free energy difference between the coagulated and fragmented states, and comparison of this energy difference with the typical thermal energy kT. The analysis reveals that fragmentation was found to be much more likely for a partially encapsulated particle than a completely encapsulated particle. In particular, it was found that thermal fragmentation was much more likely when the volume ratio of the two liquid droplets that constitute the composite particle are very different. Conversely, when the two liquid droplets are of similar volumes, the probability of thermal fragmentation is small. It is also demonstrated that the Gibbs free energy difference between the coagulated and fragmented states is not the only important factor determining the probability of thermal fragmentation of composite liquid particles. The second essential factor is the actual structure of the composite particle. It is shown that the probability of thermal fragmentation is also strongly dependent on the distance that each of the liquid droplets should travel to reach the fragmented state. In particular, if this distance is larger than the mean free path for the considered droplets in the air, the probability of thermal fragmentation should be negligible. In particular, it follows form here that fragmentation of the composite particle in the state with complete encapsulation is highly unlikely because of the larger distance that the two droplets must travel in order to separate. The analysis of composite liquid particles with the interfacial parameters that are expected in combustion aerosols demonstrates that thermal fragmentation of these vi particles may occur, and this mechanism may play a role in the evolution of combustion aerosols. Conditions for thermal fragmentation to play a significant role (for aerosol particles other than those from motor vehicle exhaust) are determined and examined theoretically. Conditions for spontaneous transformation between the states of composite particles with complete and partial encapsulation are also examined, demonstrating the possibility of such transformation in combustion aerosols. Indeed it was shown that for some typical components found in aerosols that transformation could take place on time scales less than 20 s. The analysis showed that factors that influenced surface and interfacial tension played an important role in this transformation process. It is suggested that such transformation may, for example, result in a delayed evaporation of composite particles with significant water component, leading to observable effects in evolution of combustion aerosols (including possible local humidity maximums near a source, such as a busy road). The obtained results will be important for further development and understanding of aerosol physics and technologies, including combustion aerosols and their evolution near a source.

Halogen bonding between an isoindoline nitroxide and 1,4-diiodotetrafluorobenzene: new tools and tectons for self-assembling organic spin systems

Halogen bonding has been observed for the first time between an isoindoline nitroxide and an iodoperfluorocarbon (see figure), which cocrystallize to form a discrete 2:1 supramolecular compound in which NO.⋅⋅⋅I halogen bonding is the dominant intermolecular interaction. This illustrates the potential use of halogen bonding and isoindoline nitroxide tectons for the assembly of organic spin systems...

Exploiting the 1,2,3-triazolium motif in anion-templated formation of a bromide-selective rotaxane host assembly

Stimulated by the efficacy of copper (I) catalysed Huisgen-type 1,3-dipolar cycloaddition of terminal alkynes and organic azides to generate 1,4-disubstituted 1,2,3-triazole derivatives, the importance of ‘click’ chemistry in the synthesis of organic and biological molecular systems is ever increasing.[1] The mild reaction conditions have also led to this reaction gaining favour in the construction of interlocked molecular architectures.[2-4] In the majority of cases however, the triazole group simply serves as a covalent linkage with no function in the resulting organic molecular framework. More recently a renewed interest has been shown in the transition metal coordination chemistry of triazole ligands.[3, 5, 6] In addition novel aryl macrocyclic and acyclic triazole based oligomers have been shown to recognise halide anions via cooperative triazole C5-H….anion hydrogen bonds.[7] In light of this it is surprising the potential anion binding affinity of the positively charged triazolium motif has not, with one notable exception,[8] been investigated. With the objective of manipulating the unique topological cavities of mechanically bonded molecules for anion recognition purposes, we have developed general methods of using anions to template the formation of interpenetrated and interlocked structures.[9-13] Herein we report the first examples of exploiting the 1,2,3-triazolium group in the anion templated formation of pseudorotaxane and rotaxane assemblies. In an unprecedented discovery the bromide anion is shown to be a superior templating reagent to chloride in the synthesis of a novel triazolium axle containing [2]rotaxane. Furthermore the resulting rotaxane interlocked host system exhibits the rare selectivity preference for bromide over chloride...

Proteasome inhibitors as anti-cancer agents

The ubiquitin (Ub)-proteasome pathway is the major nonlysosomal pathway of proteolysis in human cells and accounts for the degradation of most short-lived, misfolded or damaged proteins. This pathway is important in the regulation of a number of key biological regulatory mechanisms. Proteins are usually targeted for proteasome-mediated degradation by polyubiquitinylation, the covalent addition of multiple units of the 76 amino acid protein Ub, which are ligated to 1-amino groups of lysine residues in the substrate. Polyubiquitinylated proteins are degraded by the 26S proteasome, a large, ATP-dependent multicatalytic protease complex, which also regenerates monomeric Ub. The targets of this pathway include key regulators of cell proliferation and cell death. An alternative form of the proteasome, termed the immunoproteasome, also has important functions in the generation of peptides for presentation by MHC class I molecules. In recent years there has been a great deal of interest in the possibility that proteasome inhibitors, through elevation of the levels of proteasome targets, might prove useful as a novel class of anti-cancer drugs. Here we review the progress made to date in this area and highlight the potential advantages and weaknesses of this approach.

Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from freeDNAwere present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase.

Transmission X-ray microscopy : a new tool in clay mineral floccules characterization

Effective flocculation and dewatering of mineral processing streams containing clays are microstructure dependent in clay-water systems. Initial clay flocculation is crucial in the design and for the development of a new methodology of gas exploitation. Microstructural engineering of clay aggregates using covalent cations and Keggin macromolecules have been monitored using the new state of the art Transmission X-ray Microscope (TXM) with 60 nm tomography resolution installed in a Taiwanese synchrotron. The 3-D reconstructions from TXM images show complex aggregation structures in montmorillonite aqueous suspensions after treatment with Na+, Ca2+ and Al13 Keggin macromolecules. Na-montmorillonite displays elongated, parallel, well-orientated and closed-void cellular networks, 0.5–3 μm in diameter. After treatment by covalent cations, the coagulated structure displays much smaller, randomly orientated and openly connected cells, 300–600 nm in diameter. The average distances measured between montmorillonite sheets was around 450 nm, which is less than half of the cell dimension measured in Na-montmorillonite. The most dramatic structural changes were observed after treatment by Al13 Keggin; aggregates then became arranged in compacted domains of a 300 nm average diameter composed of thick face-to-face oriented sheets, which forms porous aggregates with larger intra-aggregate open and connected voids.

The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule

IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme-inhibitor complex. The inhibitor (abbreviated 4μ8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings.