Strategies and methods for the attachment of amino acids and peptides to chiral [n]polynorbornane templates

A versatile synthesis of amino acid and peptide functionalised [n]polynorbornane scaffolds is described. The frameworks are constructed using the stereoselective and regioselective cycloaddition of suitably functionalised chiral cyclobutene epoxides with similar norbornenes. The strategies employed allow a range of topologies to be accessed and a number of regioselectively addressable linkage points to be accommodated.     

Hemiaminals as substrates for sulfur ylides: direct asymmetric syntheses of functionalised pyrrolidines and piperidines

Phenyl stabilised chiral sulfur ylides react with five-membered-ring hemiaminals to give functionalised pyrrolidines directly with high enantioselectivity. The reaction can be diverted to give piperidines instead by isolation of the intermediate epoxide and treatment with TMSOTf.     

Functionalisation of aldehydes via aerobic hydroacylation of azodicarboxylates 'on' water

Herein we report the functionalisation of aldehydes via hydroacylation of azodicarboxylates. A range of functionalised aldehydes are employed as the limiting reagent including chiral non-racemic aldehydes bearing α-stereocentres which are functionalised giving access to enantiomerically pure products. The resultant hydrazides can be employed as acyl donors in the synthesis of amides.     

Organocatalytic asymmetric transformations of modified Morita-Baylis-Hillman adducts

Chiral Lewis basic tertiary amines or phosphines can enable properly modified Morita-Baylis-Hillman (MBH) adducts to undergo asymmetric allylic substitutions with a wide range of nucleophiles. In addition, assisted by a Br?nsted base, chiral Lewis bases can also catalytically convert modified MBH adducts into allylic ylides, which can be engaged in a variety of asymmetric annulation reactions. This tutorial review will focus on such chiral Lewis base-catalysed asymmetric transformations of MBH adducts, especially those developed over the past five years, allowing for the rapid construction of densely functionalised chiral molecules with high levels of regio- and stereoselectivities.     

Solvent- and temperature-dependent functionalisation of enantioenriched aziridines

A highly stereo‐ and regioselective functionalisation of chiral non‐racemic aziridines is reported. By starting from a parent enantioenriched aziridine and finely tuning the reaction conditions, it is possible to address the regio‐ and stereoselectivity of the lithiation/electrophile trapping sequence, thereby allowing the preparation of highly enantioenriched functionalised aziridines. From chiral N‐alkyl trans‐2,3‐diphenylaziridines (S,S)‐ 1 a , b , two differently configured chiral aziridinyllithiums could be generated (trans‐ 1 a , b‐Li in toluene and cis‐ 1 a , b‐Li in THF), thus disclosing a solvent‐dependent reactivity that is useful for the synthesis of chiral tri‐substituted aziridines with different stereochemistry. In contrast, chiral aziridine (S,S)‐ 1 c showed a temperature‐dependent reactivity to give chiral ortho‐lithiated aziridine 1 c‐ ortho ‐Li at ?78 °C and α‐lithiated aziridine 1 c‐α‐Li at 0 °C. Both lithiated intermediates react with electrophiles to give enantioenriched ortho‐ and α‐functionalised aziridines. The reaction of all the lithiated aziridines with carbonyl compounds furnished useful chiral hydroxyalkylated derivatives, the stereochemistry of which was ascertained by X‐ray and NMR spectroscopic analysis. The usefulness of chiral non‐racemic functionalised aziridines has been demonstrated by reductive ring‐opening reactions furnishing chiral amines that bear quaternary stereogenic centres and chiral 1,2‐, 1,3‐ and 1,5‐aminoalcohols. It is remarkable that the solvent‐dependent reactivity observed with (S,S)‐ 1 a , b permits the preparation of both the enantiomers of amines ( 11 and ent‐ 11 ) and 1,2‐aminoalcohols ( 13 and ent‐ 13 ) starting from the same parent aziridine. Interestingly, for the first time, a configurationally stable chiral α‐lithiated aziridine ( 1 c‐α‐Li ) has been generated at 0 °C. In addition, ortho‐hydroxyalkylated aziridines have been easily converted into chiral aminoalkyl phthalans, which are useful building blocks in medicinal chemistry.     

Synthesis of Chemically Asymmetric Silica Nanobottles and Their Application for Cargo Loading and as Nanoreactors and Nanomotors

We report the synthesis of chemically asymmetric silica nanobottles (NBs) with a hydrophobic exterior surface (capped with 3‐chloropropyl groups) and a hydrophilic interior surface for spatially selective cargo loading, and for application as nanoreactors and nanomotors. The silica NBs, which have a “flask bottle” shape with an average diameter of 350 nm and an opening of ca. 100 nm, are prepared by anisotropic sol–gel growth in a water/n‐pentanol emulsion. Due to their chemically asymmetric properties, nanoparticles (NPs) with hydrophilic or hydrophobic surface properties can be selectively loaded inside the NBs or on the outside of the NBs, respectively. A high‐performance nanomotor is constructed by selectively loading catalytically active hydrophilic Pt NPs inside the NBs. It is also demonstrated that these NBs can be used as vessels for various reactions, such as the in situ synthesis of Au NPs, and using Au NP‐loaded NBs as nanoreactors for catalytic reactions.     

Copper‐Catalyzed Asymmetric Conjugate Addition with Chiral SimplePhos Ligands

SimplePhos ligands represent a novel class of monodentate chiral ligands based on a chiral amine moiety and flexible diaryl groups on the phosphorous atom. They can be easily prepared by two different pathways and they can be highly functionalised. Herein we report the copper‐catalysed asymmetric conjugate addition of diethyl zinc and trialkylaluminium reagents with SimplePhos ligands, which gives high enantioselectivity with cyclic enones, acyclic enones and nitro‐olefins, with up to 98.6 % ee. Of particular interest is the reaction of trialkylaluminium reagents with a wide range of 3‐substituted enones, thus allowing the formation of stereogenic quaternary carbon centres.     

稳定于碳纳米管的Pt高价态物种在不对称氢化反应中的作用

碳纳米管的独特性质,特别是其一维有序的管腔结构所形成的限域环境在催化反应中的应用引起了广泛的兴趣.已有将常规的液相氢化反应和气相反应限域于碳纳米管内的研究报道,并且大多数的研究结果显示限域于碳纳米管内的反应活性和/或选择性有明显提高,但多数研究没有对此给出清晰的解释.金鸡纳碱修饰的Pt催化剂催化的α-酮酸酯不对称氢化体系被认为是多相不对称催化领域发展的里程碑.早期的研究是简单的将碳纳米管作为Pt催化剂的载体用于α-酮酸酯不对称氢化反应,取得了中等的活性和对映体选择性.我们研究组发展了一种催化剂制备方法,可选择性的将Pt纳米粒子限域于碳纳米管管腔内或担载在碳纳米管管外,并将所制备的碳纳米管Pt催化剂应用于α-酮酸酯多相不对称催化反应中,发现封装于管腔内的管内型Pt纳米粒子的催化性能显著高于负载在管腔外壁的管外型Pt纳米粒子的催化性能.然而,对于管内型Pt催化剂催化性能增强的原因并不清楚. CO化学吸附和高分辨投射电镜(HRTEM)的表征结果表明管腔内外的Pt纳米粒子的大小和形貌没有明显区别.本论文在上述研究基础上,采用X射线光电子能谱(XPS),氢气程序升温脱附(H2-TPD),紫外可见光谱(UV-Vis)等表征手段研究了Pt纳米粒子担载于碳纳米管内和管外形成的催化剂在α-酮酸酯的不对称氢化反应中催化性能差异的原因. XPS测试结果表明,管内型和管外型Pt催化剂的载体的碳物种分布没有显出差异,但催化活性中心Pt纳米粒子的Pt物种组成不同.经225 oC H2还原后管外型Pt催化剂不存在高氧化态的Pt物种,而管内型Pt催化剂在400 oC H2还原仍然具有7%的高氧化态Pt物种.相应的催化反应结果表明,具有这种稳定的高氧化态Pt物种有利于获得高对映体选择性.参比催化剂商业化的Pt/AC和Pt/Al2O3的XPS测试结果也表明,对映体选择性高的Pt/Al2O3催化剂具有较高含量的高氧化态Pt物种.同时我们发现高氧化态Pt物种有利于催化剂对手性修饰剂和反应底物的吸附.虽然文献中一般认为Pt0是该反应的活性中心,但我们认为这些高氧化态的Pt物种有利于纳米粒子和手性修饰剂之间的相互作用,从而提高反应的对映选择性.我们进一步研究了表明高氧化态的Pt物种能存在于碳纳米管管腔内的原因.发现在催化剂制备过程中所使用的还原剂甲酸钠中残留的钠离子能稳定碳纳米管管腔内高氧化态Pt物种.我们采用H2直接还原制备了不含钠离子的参比管内型Pt催化剂.该参比催化剂的对映体选择性与管外型Pt催化剂相当,明显低于管内型Pt催化剂.同时该参比催化剂对手性修饰剂和底物的吸附能力弱于管内型Pt催化剂.以上结果清晰的表明了碳纳米管内由钠离子稳定的高氧化态Pt物种在α-酮酸酯多相不对称催化反应中的重要作用.然而,我们发现高氧化态Pt+物种含量的差异并不能很好的解释管内型和管外型Pt催化剂反应活性的差异. H2-TPD的结果表明相比于管外型Pt纳米粒子催化剂,管内型Pt纳米粒子具有更高的活化氢分子的能力,相应的催化反应结果表明,管外型Pt催化剂的反应活性随H2压力的降低而显著降低,而管内型Pt催化剂在0.1 MPa H2条件下仍然具有较高活性.简单的动力学模拟结果表明,在0.1 MPa H2条件下,碳纳米管管腔能显著富集H2.     

Synthesis of bioactive indolocarbazoles: synthesis, nucleophilic ring-opening and chiral base desymmetrisation of a cyclic sulfate intermediate

A number of new functionalised bridged indolocarbazole systems have been prepared by ring-opening reactions of a key cyclic sulfate intermediate, prepared from the corresponding diol by the action of sulfuryl diimidazole and DBU. The same cyclic sulfate also undergoes an unprecedented asymmetric rearrangement to a chiral ketone, on treatment with a chiral lithium amide base.     

Novel and Efficient Resolution of 1,1'-Bi-2-naphthol and Synthesis of Optically Pure Unsymmetrically Substituted Binaphthyls

Both enantiomers of 1, 1'-Bi-2-naphthol (BINOL) 1 are important chiral ligands and auxiliaries for a number of asymmetric transformations such as aldol condensations, alkylations, Diels-Alder reactions, Michael additions, epoxidations, etc. Optically pure 1 and their derivatives have also been used extensively in chiral recognition, chiral separation and construction of functionalised materials^[1]. As a result the development of efficient and economic methods for the preparation of optically pure 1 has attracted much attention in recent years^[2] and novel methods for the resolution of racemic 1 (Rac-1) continue to be developed.     

Homogeneous Dielectric Barrier Discharge Reactor with Two L-Shaped Electrodes Operating at Atmospheric Pressure

Homogeneous non-thermal plasma at atmospheric pressure is highly effective for surface treatment of various polymeric substrates. We propose a dielectric barrier discharge (DBD) reactor consisting of two back-to-back L-shaped electrodes, driven by bipolar voltage pulses of opposite polarity. This structure and driving scheme allow the discharge to be initiated earlier inside the reactor than outside the reactor. The plasma formed inside the reactor is ejected through a slit and moves toward the substrate. As a result, an abundance of electrons is provided to the outside region of the reactor at its breakdown stage. These electrons play a role in suppressing the filamentary mode, and hence, homogeneous discharge in He and Ar can be achieved under an open air configuration. The discharge characteristics inside and outside the reactor are analyzed by using the discharge current and the temporal evolution of emission intensity, respectively. The importance of seed electrons available at the gas breakdown stage in achieving a homogeneous discharge is discussed together with the differences between the discharge characteristics of helium and argon gases.     

The electrochemical polymerisation of a [2]rotaxane

We report the synthesis of a dithienylpyrrole-stoppered rotaxane and its subsequent electrochemical polymerisation onto a platinum working electrode surface. We have shown that the tetracationic cyclophane moiety of the rotaxane does not impair electropolymerisation of this derivative. Indeed, functionalised films can be conveniently prepared by oxidative polymerisation of the dithienylpyrrole stopper units, to yield a network of rotaxane units interconnected by a conducting polymer backbone.     

A new organogelator based on an enantiopure C2 symmetric pyrrolidine

The synthesis and the properties of a new chiral organogelator based on a C(2) symmetric pyrrolidine, are described together with its use for the synthesis of other functionalised organogelators.     

Cell-specific internalization study of an aptamer from whole cell selection

Nucleic acid aptamers have been shown many unique applications as excellent probes in molecular recognition. However, few examples are reported which show that aptamers can be internalized inside living cells for aptamer functional studies and for targeted intracellular delivery. This is mainly due to the limited number of aptamers available for cell-specific recognition, and the lack of research on their extra- and intracellular functions. One of the major difficulties in aptamers' in vivo application is that most of aptamers, unlike small molecules, cannot be directly taken up by cells without external assistance. In this work, we have studied a newly developed and cell-specific DNA aptamer, sgc8. This aptamer has been selected through a novel cell selection process (cell-SELEX), in which whole intact cells are used as targets while another related cell line is used as a negative control. The cell-SELEX enables generation of multiple aptamers for molecular recognition of the target cells and has significant advantages in discovering cell surface binding molecules for the selected aptamers. We have studied the cellular internalization of one of the selected aptamers. Our results show that sgc8 is internalized efficiently and specifically to the lymphoblastic leukemia cells. The internalized sgc8 aptamers are located inside the endosome. Comparison studies are done with the antibody for the binding protein of sgc8, PTK7 (Human protein tyrosine kinase-7) on cell surface. We also studied the internalization kinetics of both the aptamer and the antibody for the same protein on the living cell surface. We have further evaluated the effects of sgc8 on cell viability, and no cytotoxicity is observed. This study indicates that sgc8 is a promising agent for cell-type specific intracellular delivery.     

Quantifying the Effect of Surface Ligands on Dendron–DNA Interactions: Insights into Multivalency through a Combined Experimental and Theoretical Approach

We report the synthesis, DNA binding ability and preliminary gene delivery profiles of dendrons with different amine surface groups, 1,3‐diaminopropane (DAP), N,N‐di‐(3‐aminopropyl)‐N‐(methyl)amine (DAPMA) and spermine (SPM). By using a combination of ethidium bromide displacement, gel electrophoresis and transfection assays, it is shown that the dendrons with SPM groups are the most effective DNA binders, while the DAPMA‐functionalised dendrons were the most effective systems for gene delivery (although the gene delivery profiles were still modest). In order to provide deeper insight into the experimental data, we performed a molecular dynamics simulation of the interactions between the dendrons and DNA. The results of these simulations demonstrated that, in general terms, the enthalpic contribution to binding was roughly proportional to the dendron surface charge, but that dendrons with DAP (and DAPMA) surface amines had significant entropic costs of binding to DNA. In the case of DAP, this is a consequence of the fact that the entire dendron structure has to be organised in order for each individual monoamine charge to make effective contact with DNA. For SPM, however, each surface ligand is already a multivalent triamine, therefore, each individual charge has a much lower entropic cost of binding. For DAPMA, we observed that strong binding of the hindered tertiary amine to the DNA double helix led to ligand back‐folding and significant geometric distortion of DNA. Although this weakens the overall binding, we suggest that this distortion might be an explanation for the experimentally observed enhanced gene delivery, in which DNA compaction is an important step. Overall, this paper demonstrates how structure–activity relationships can be developed for multivalent dendritic ligands and provides insights into the thermodynamics of multivalent interactions.     

SPE and purification of DNA using magnetic particles

Superparamagnetic particles have been attractive for molecular diagnostics and analytical chemistry applications due to their unique magnetic properties and their ability to interact with various biomolecules of interest. This paper presents a critical overview of magnetic nano ‐ and microparticles used as a solid phase for extraction and purification of DNAs. The mechanisms of DNA binding to the surface of functionalised magnetic particles are described. The most widely used materials including silica supports, organic polymers and other materials, mostly containing magnetite or paramagnetic metallic elements are reviewed. The main application areas of magnetic particles for DNA separation are briefly described.     

Expanding the Scope of Enantioselective FerroPHANE‐Promoted [3+2] Annulations with α,β‐Unsaturated Ketones

The planar chiral 2‐phospha[3]ferrocenophane I has been shown to be the first efficient nucleophilic organocatalyst for the enantioselective synthesis of cyclopentenylphosphonates, through [3+2] cyclizations between diethyl allenylphosphonate and α,β‐unsaturated ketones. The same catalyst has also been applied to the highly enantioselective [3+2] cyclizations of allenic esters with dibenzylideneacetone and analogous bis‐enones, leading to functionalised cyclopentenes with either monocyclic or spirocyclic structures (ee 84–95 %). It has been shown that the residual enone functions in the resulting cyclopentenes can be involved in subsequent cyclization steps to afford unprecedented C₂‐symmetric bis‐cyclopentenylketones. In order to provide insight into the behaviour of FerroPHANE I as a chiral catalyst in [3+2] cyclisations, the energetically most favoured isomers of the key phosphine‐allene adduct have been calculated by DFT methods. Factors likely to control the chiral induction process are highlighted.     

Donnan potential and surface potential of a spherical soft particle in an electrolyte solution

A simple numerical method, which does not involve numerical integration of the Poisson-Boltzmann equations, is presented for obtaining the relationship between the Donnan potential and surface potential of a spherical soft particle (i.e., a polyelectrolyte-coated particle) in a symmetrical electrolyte solution. We assume that a soft particle consists of the particle core of radius a covered with an ion-penetrable surface layer of polyelectrolytes of thickness d and that ionized groups of valence Z are distributed at a uniform density of N in the polyelectrolyte layer and the relative permittivity takes the same value in the regions outside and inside the polyelectrolyte layer. The Donnan potential and surface potential are determined by the values of a, d, Z, N, and the Debye-Hückel parameter kappa of the electrolyte solution. Numerical results obtained by the present method are in excellent agreement with exact results obtained by solving the nonlinear spherical Poisson-Boltzmann equations for the both regions inside and outside the polyelectrolyte layer.     

Dendritic phosphoramidite ligands in Rh-catalysed asymmetric hydrogenations

The axially chiral BICOL backbone was functionalised with two third generation carbosilane dendritic wedges and further elaborated to a phosphoramidite ligand. High enantioselectivities were obtained when these monodentate ligands were applied in the rhodium-catalysed asymmetric hydrogenation of methyl 2-acetamidocinnamate.     

Effect of catalyst confinement and pore size on Fischer-Tropsch synthesis over cobalt supported on carbon nanotubes

This paper studies the impact of structure of cobalt catalysts supported on carbon nanotubes(CNT) on the activity and product selectivity of Fischer-Tropsch synthesis(FTS) reaction.Three types of CNT with average pore sizes of 5,11,and 17 nm were used as the supports.The catalysts were prepared by selectively impregnating cobalt nanoparticles either inside or outside CNT.The TPR results indicated that the catalyst with Co particles inside CNT was easier to be reduced than those outside CNT,and the reducibility of cobalt oxide particles inside the CNT decreased with the cobalt oxide particle size increasing.The activity of the catalyst with Co inside CNT was higher than that of catalysts with Co particles outside CNT.Smaller CNT pore size also appears to enhance the catalyst reduction and FTS activity due to the little interaction between cobalt oxide with carbon and the enhanced electron shift on the non-planar carbon tube surface.