Cationic and fluorescent "Janus" dendrimers

Two synthetic routes to "Janus"-type dendrimers possessing ammonium groups on one side and fluorescent dansyl derivatives on the other side are described. These surface-block dendrimers are obtained by the coupling of two different dendrons, built from the hexafunctional cyclotriphosphazene core. Their characterization and their photophysical behavior are reported. The largest compound possesses 10 ammonium groups and 5 dansyl groups; it is potentially useful as a fluorescent label in materials science and biology.     

"Clickable" polymersomes

Polymersomes, composed of amphiphilic polystyrene-block-poly(acrylic acid) (PS-b-PAA), with the periphery being covered with azide groups, were used for further functionalization using "click" chemistry.     

"Schizoid" reactivity of 1,1'-diisocyanoferrocene

The two chemically equivalent functional groups of 1,1'-diisocyanoferrocene each undergo a different specific reaction with the gold(I) acetylide [Au(C=C-Fc)], viz. ordinary coordination and extraordinary 1,1-insertion.     

钢都酒的香味成分分析

通过对钢都酒进行化学处理,分类收集组分,采用GC-MS联用技术对各组分进行分离与定性定量测定,分离并鉴定出35个化合物,并确定了酒的香型。     

Access to "Friedel-Crafts-restricted" tert-alkyl aromatics by activation/methylation of tertiary benzylic alcohols

Herein we describe a two-step protocol to prepare m-tert-alkylbenzenes. The appropriate tertiary benzylic alcohols are activated with SOCl(2) or concentrated HCl and then treated with trimethylaluminum, affording the desired products in 68-97% yields (22 examples). This reaction sequence is successful in the presence of a variety of functional groups, including acid-sensitive and Lewis-basic groups. In addition to t-Bu groups, 1,1-dimethylpropyl and 1-ethyl-1-methylpropyl groups can also be installed using this method.     

"Lego" chemistry for the straightforward synthesis of dendrimers

A new straightforward method of synthesis of dendrimers, using two branched monomers (CA(2) and DB(2)), is described. Each generation is obtained in a single quantitative step, with only N(2) or H(2)O as byproducts; generation 4 is obtained in only four steps. The end groups are alternatively phosphines and hydrazines; their versatile reactivity is illustrated by the reaction of generation 4 with a branched CD(5) monomer, which increases the number of end groups in a single step from 48 to 250.     

Dramatic increase of quench efficiency in "spacerless" dimaleimide fluorogens

In this post-genomic era, new techniques are needed to cope with the task of assigning functional roles to the huge number of identified putative gene products. We have developed a minimalist labelling strategy based on the use of synthetic fluorogenic probe reagents that fluoresce only after their reaction with a target peptide sequence. The probe reagents have fluorescent cores and bear two maleimide groups, such that their latent fluorescence is quenched by a photoinduced electron transfer (PET) to the pendant maleimide groups, until both of these groups undergo a specific thiol addition reaction. The efficiency of the fluorescence quenching is critical to the practicality of this labelling method, and has been predicted to be related to the intramolecular distance between the fluorophore and the maleimide groups. We have conducted the first direct test of this hypothesis by preparing a series of novel fluorogens that differ only by the spacer moiety separating their coumarin fluorophore and their dimaleimide fragment. A striking correlation was observed between intramolecular distance and the fluorescence enhancement (FE) observed after reaction with two equivalents of thiol. Guided by this observation, we then designed 'spacerless' fluorogens, of which a dansyl derivative shows an FE ratio of >300, the largest recorded for dimaleimide fluorogens. The trends observed herein provide valuable lessons for subsequent fluorogen design, and the novel fluorogens developed in the course of this study are currently being applied to protein labelling applications.     

"Super armed" glycosyl donors: conformational arming of thioglycosides by silylation

Glycosyl donors protected with bulky silyl protective groups (tert-butyldimethylsilyl, TBS), on the 2-, 3-, and 4-OH groups were found to have superior reactivity compared with benzylated thioglucosides. The enhanced reactivity is explained by the stereoelectronic effects associated with the conformational change induced by the silylation. A TBS silylated thioglucoside donor has axial OR groups, whereas a benzylated thioglucoside has equatorial OR groups, leading to much more favorable charge-dipole interactions in the transition state. This concept could be used to create "super armed" glucosyl, mannosyl, rhamnosyl, and galactosyl donors, which could cross-couple with the armed acceptors, phenyl 2,3,4-tri-O-benzyl-beta-D-thioglucoside or phenyl 2,3,6-tri-O-benzyl-beta-D-thioglucoside, to give the corresponding armed disaccharides in good to excellent yields.     

"Clickable" pillar[5]arenes

Introduction of bulky substituents such as benzyl and pyrenyl groups using click reactions inhibited or slowed the rotation of the units on the NMR chemical shift timescale. The perpyrenylated pillar[5]arene showed a thermally-responsive excimer emission, but a unit model of the perpyrenylated pillar[5]arene did not exhibit such a response.     

A "classical" tetrahydroxycalix[4]arene adopting the 1,2-alternate conformation

The first example of a "classical" tetrahydroxycalixarene, which adopts the 1,2-alternate conformation both in solution and in the crystal, is described. Calixarene derivatives with two distal methylene groups substituted in a trans fashion by phenyl (5a) or mesityl (5b) groups were synthesized via addition of PhMgBr/CuCN or MesMgBr/CuCN to the bis(spirodiene) derivative 3. Whereas the phenyl-substituted calixarene derivative 5a adopts the usual "cone" conformation, solution NMR data and X-ray crystallography indicate that the more crowded mesityl derivative 5b adopts a 1,2-alternate conformation with the two mesityl groups located at isoclinal positions of the macrocycle.     

"Clickable" metal-organic framework

We demonstrated the metal-organic framework bearing the azide group in the organic linkers and in situ click reactions with some small alkynes. The XRPD patterns indicated that the click reaction proceeded without any decomposition of the original MOF network. Controlling the organic linkers and incorporation of the azide groups should provide the designer-made MOFs that have controlled molecular cavities with the desired steric dimensions and functionality.     

"Chemical ligation": a versatile method for nucleoside modification with boron clusters

A general approach to the synthesis of nucleoside conjugates containing carborane and metallocarborane complexes, based on Huisgen 1,3-dipolar cycloaddition ("chemical ligation"), is described. Boron-cluster-donors bearing terminal azide or ethynyl groups were prepared in the ring-opening reaction of dioxane-boron-cluster adducts and an azide anion or suitable alkynol-derived alcoholate nucleophile. Analogous derivatives bearing terminal sulfhydryl groups were also prepared. Nucleosides with various spacers containing terminal azide or ethynyl groups, located within nucleobases or sugar residues, were used as boron-cluster acceptors. The proposed methodology provides a convenient way to synthesize libraries of boron-cluster-modified nucleosides for various applications.     

Azide-derivatized gold nanorods: functional materials for "click" chemistry

We describe herein the synthesis of functional gold nanorods suitable for carrying out "click" chemistry reactions. Gold nanorods modified with a copolymer containing sulfonate and maleic acid groups have been conjugated to a bifunctional azide molecule (amine-PEG-azide). The maleic acid molecules in the copolymer participate in carbodiimide-mediated amide bond formation with amine groups of the azide linker, whereas the sulfonate groups prevent nanorod aggregation in water. Spectroscopic and zeta-potential measurements have been used to confirm the successful surface modification of the gold nanorods. These azide-functionalized nanorods can carry out chemical reactions based on click chemistry. As a case study, we have demonstrated the "clicking" of azide-nanorods to an acetylene-functionalized enzyme, trypsin, by a copper-catalyzed 1,3-dipolar cycloaddition reaction. The enzyme is not only stable after bioconjugation but is also biologically active, as demonstrated by its digestion of the protein casein. For comparison, the biological activity of trypsin conjugated to gold nanorods by two other commonly used methods (carbodiimide-mediated covalent attachment via amide bond formation and simple electrostatic adsorption) has been studied. The enzyme conjugated by click chemistry demonstrates improved biological activity compared with other forms of bioconjugation. This general and simple approach is easy, specific with higher yields, environmentally benign, and applicable to a wide range of analytes and biomolecules.     

"Fingertip"-guided noncovalent functionalization of carbon nanotubes by dendrons

Noncovalent functionalization of carbon nanotubes (CNTs) by dendrons was demonstrated. Certain types of dendrons successfully functionalized CNT surfaces through the noncovalent interactions between the peripheries of the dendrons and the sidewalls of CNTs. Dendrons have a unique anisotropic shape and an orthogonal functional group at their apex, and thus can generate a certain spacing between the functional groups upon immobilization on surfaces. Atomic force microscope (AFM) imaging, dispersion experiments, and MicroRaman spectroscopy were employed for the characterization of the functionalization. The binding was found to be governed by the chemical nature of the terminal groups, namely, the "fingertips", through a comparison study on the adsorption efficiency of the dendron analogs. Functional groups such as the carboxylic acid group and the benzyl amide group were effective for the cooperative binding. AFM analysis showed that the average spacing generated by the dendrons was 14-15 nm at a particular adsorption condition. Assembling streptavidin on the tubes through the dendrons and biotin confirmed the realization of the regulated spacing as well as the elimination of unwanted aggregation. The noncovalent functionalization of CNTs by a dendron can be a new approach toward sensible nanobiodevices, not only by introducing biomolecular probes on CNTs without disruption of the electronic network of the tubes, but also by providing the immobilized probe molecules with a space ample enough to minimize steric hindrance for the unhindered interaction with their target species.     

"Polar patch" proteases as glycopeptiligases

The strategy of combined site directed mutagenesis and chemical modification with polar prosthetic groups was used to broaden substrate specificity of proteases resulting in the first successful formation of glycopeptides through the use of glucoamino acid acyl donors in yields of up to 90%.     

"Turn-on" fluorescent sensing with "reactive" probes

Chemical probes are valuable tools for the investigation of biochemical processes, diagnosis of disease markers, detection of hazardous compounds, and other purposes. Therefore, the development of chemical probes continues to grow through various approaches with different disciplines and design strategies. Fluorescent probes have received much attention because they are sensitive and easy-to-operate, in general. To realize desired selectivity toward a given analyte, the recognition site of a fluorescent probe is designed in such a way to maximize the binding interactions, usually through weak molecular forces such as hydrogen bonding, toward the analyte over other competing ones. In addition to such a supramolecular approach, the development of fluorescent probes that sense analytes through chemical reactions has witnessed its usefulness for achieving high selectivity, in many cases, superior to that obtainable by the supramolecular approach. Creative incorporations of the reactive groups to latent fluorophores have provided novel chemical probes for various analytes. In this feature article, we overview the recent progress in the development of turn-on fluorescent probes that are operating through chemical reactions triggered by target analytes. Various chemical reactions have been implemented in the development of many reactive probes with very high selectivity and sensitivity toward target analytes. A major emphasis has been focused on the type of chemical reactions utilized, with the hope that further explorations can be made with new chemical reactions to develop reactive probes useful for various applications.     

Molecular "compasses" and "gyroscopes." III. Dynamics of a phenylene rotor and clathrated benzene in a slipping-gear crystal lattice

Samples of 1,4-bis(3,3,3-triphenylpropynyl)benzene 3 were prepared by Pd(0)-catalyzed coupling of 3,3,3-triphenylpropyne (1) and 1,4-diiodobenzene. The structure of compound 3 is such that the central phenylene can play the role of a gyroscope wheel, while the alkyne bond and trityl groups can act as an axle and shielding frameworks, respectively. Crystals grown from benzene and dichloromethane were characterized by X-ray diffraction, variable-temperature (13)C CPMAS NMR, quadrupolar echo solid-state (2)H NMR, and thermal analyses. The rotational dynamics of benzene molecules and phenylene groups were characterized in terms of 6-fold rotation and 2-fold flipping models, respectively. The possibility of a gearing mechanism between adjacent benzene molecules and phenylene groups suggested by the clathrate structure was investigated. However, it was found that 6-fold rotation of benzene molecules at 300 K occurs in the gigahertz regime (or higher) and 2-fold flipping of phenylene groups in the kilohertz range in a structure that can be described as a slipping-gear lattice. The rotational dynamics of the phenylene group in the solvent-free structure were remarkably similar to those in the clathrate, and both are among the fastest known for phenylene rotation in solids. The results presented here provide a valuable starting point for the design and analysis of crystalline solids with correlated molecular motions.     

Synthesis, electrochemistry, and interactions with beta-cyclodextrin of dendrimers containing a single ferrocene subunit located "off-center"

Two series of dendrimers containing a single ferrocene unit located in the focal point of these macromolecules have been synthesized and characterized. The first series of dendrimers has considerable lipophilic character, with tert-butyl ester groups located in their peripheral regions. In contrast, the second series of dendrimers was obtained by the hydrolysis of these peripheral ester groups, yielding water-soluble dendrimers with carboxylic acid groups in their surfaces. The electrochemical properties of these macromolecules were strongly affected by the dendritic groups attached to the ferrocene subunits. Host-guest interactions between the water-soluble dendrimers and the well-known receptor beta-cyclodextrin were also investigated. The dendritic groups were found to hamper markedly the formation of inclusion complexes between the cyclodextrin receptor and the dendrimer's ferrocene unit.     

Synthesis of 3-miktoarm stars and 1st generation mikto dendritic copolymers by "living" radical polymerization and "click" chemistry

The facile synthesis of 3-miktoarm star polymers and 1st generation mikto polymeric dendrimers using atom transfer radical polymerization (ATRP) and "click" chemistry is demonstrated. ATRP was used to synthesize near uniform polymers with Br chain ends, which were easily converted into azido groups. These polymer chains were then attached to a trifunctional alkyne molecule (tripropargylamine) using click reactions in a variety of ways to make the miktoarm stars and miktoarm polymeric dendrimers.     

Synthesis and complexation of "back-to-back" capped bis-dioxocyclams

Pyridine-capped 5,12-dioxocyclams were coupled "back-to-back" directly, with one or two intervening phenyl groups, an ethynyl group, or a diazo group via Suzuki, Sonogashira, or reductive coupling of the 4-nitropyridine monocyclam. These bis-dioxocyclams linked through extended pi-conjugated systems were complexed to copper(II) and cobalt(III), producing bis-metal complexes which were characterized spectroscopically and electrochemically. These studies gave little evidence for electronic communication between metal centers across the pi-conjugated linkers.