Electronic detection of the enzymatic degradation of starch

[reaction: see text] The enzymatic degradation of starch can be monitored electronically using single-walled carbon nanotubes (SWNTs) as semiconducting probes in field-effect transistors (FETs). Incubation of these devices in aqueous buffer solutions of amyloglucosidase (AMG) results in the removal of the starch from both the silicon surfaces and the side walls of the SWNTs in the FETs, as evidenced by direct imaging and electronic measurements.     

Nanoscale borromeates

[Structure: See text] In addition to a parent zinc(II) Borromean ring (BR) complex, the preparation and characterization of two hexasubstituted BR complexes with either 4-acetoxymethylphenyl or 4-methylthiophenyl substituents associated in turn with all six pyridyl rings has been achieved convergently in good yields by appealing to the dynamic features of the reactions between primary amino groups in a preformed acyclic ligand and 2,6-diformylpyridine. Two molecules of the acyclic ligands react with two molecules of 2,6-diformylpyridine to form a cyclic [2 + 2] tetraimine in the presence of Zn(II) ions as templates in 2-propanol at 70 degrees C. The successful preparation of the two derivatives by convergent template-directed syntheses opens up opportunities to self-assemble, under equilibrium control, numerous nanoscale metallo-organic particles with potentially useful properties.     

Alkynenitriles: chelation-controlled conjugate additions

[reaction: see text] Chelation between gamma-hydroxybutynenitrile and Grignard reagents triggers a particularly facile anionic conjugate addition reaction. Structurally diverse Grignard reagents add with equal efficiency, providing an intermediate anion that stereoselectively alkylates benzaldehyde in an overall addition-alkylation reaction.     

A self-assembled multivalent pseudopolyrotaxane for binding galectin-1

A self-assembled pseudopolyrotaxane consisting of lactoside-displaying cyclodextrin (CD) "beads" threaded onto a linear polyviologen "string" was investigated for its ability to inhibit galectin-1-mediated T-cell agglutination. The CDs of the pseudopolyrotaxane are able to spin around the axis of the polymer chain as well as to move back and forth along its backbone to alter the presentation of its ligand. This supramolecular superstructure incorporates all the advantages of polymeric structures, such as the ability to span large distances, along with a distinctively dynamic presentation of its lactoside ligands to afford a neoglycoconjugate that can adjust to the relative stereochemistries of the lectin's binding sites. The pseudopolyrotaxane exhibited a valency-corrected 10-fold enhancement over native lactose in the agglutination assay, which was greater than the enhancements observed for lactoside-bearing trivalent glycoclusters and a lactoside-bearing chitosan polymer tested using the same assay. The experimental results indicate that supramolecular architectures, such as the pseudopolyrotaxane, provide tools for investigating protein-carbohydrate interactions.     

Ferrocene-containing carbohydrate dendrimers

Aliphatic amines, incorporating one or three (branched) acylated beta-D-glucopyranosyl residues, were coupled with the acid chloride of ferrocenecarboxylic acid and with the diacid chloride of 1,1'-ferrocenedicarboxylic acid to afford four dendrimer-type, carbohydrate-coated ferrocene derivatives in good yields (54-92%). Deprotection of the peracylated beta-D-glucopyranosyl residues was achieved quantitatively by using Zemplén conditions, affording four water-soluble ferrocene derivatives. When only one of the two cyclopentadienyl rings of the ferrocene unit is substituted, strong complexes are formed with beta-cyclodextrin in H2O, as demonstrated by liquid secondary ion mass spectrometry (LSIMS), 1H NMR spectroscopy, electrochemical measurements, and circular dichroism spectroscopy. Molecular dynamics calculations showed that the unsubstituted cyclopentadienyl ring is inserted through the cavity of the toroidal host in these complexes. The electrochemical behavior of the protected and deprotected ferrocene-containing dendrimers was investigated in acetonitrile and water, respectively. The diffusion coefficient decreases with increasing molecular weight of the compound. The potential for oxidation of the ferrocene core, the rate constant of heterogeneous electron transfer, and the rate constant for the energy-transfer reaction with the luminescent excited state of the [Ru(bpy)3]2+ complex (bpy = 2,2'-bipyridine) are strongly affected by the number (one or two) of substituents and by the number (one or three) of carbohydrate branches present in the substituents. These effects are assigned to shielding of the ferrocene core by the dendritic branches. Electrochemical evidence for the existence of different conformers for one of the dendrimers in aqueous solution was obtained.     

The effect of ion energy upon plasma polymerization deposition rate for acrylic acid

A novel technique, which allows the importance of ion energy in plasma polymer film growth to be investigated, without perturbation of any other plasma parameter (particle densities or temperatures) or, in principle, perturbation of particle (neutral or ion) fluxes is applied in the plasma polymerisation of acrylic acid and new insight into polymer formation is gleaned.     

Dynamic chirality: keen selection in the face of stereochemical diversity in mechanically bonded compounds

The template-directed syntheses, employing bisparaphenylene-[34]crown-10 (BPP34C10), 1,5-dinaphthoparaphenylene-[36]crown-10 (1/5NPPP36C10), and 1,5-dinaphtho-[38]crown-10 (1/5DNP38C10) as templates, of three [2]catenanes, whereby one of the two bipyridinium units in cyclobis(paraquat-p-phenylene) is replaced by a bipicolinium unit, are described. The crude reaction mixtures comprising the [2]catenanes all contain slightly more of the homologous [3]catenanes, wherein a "dimeric" octacationic cyclophane has the crown ether macrocycles encircling the alternating bipyridinium units with the bipicolinium units completely unfettered. X-ray crystallography, performed on all three [2]catenanes and two of the three [3]catenanes reveals co-conformational and stereochemical preferences that are stark and pronounced. Both the [3]catenanes crystallize as mixtures of diastereoisomers on account of the axial chirality associated with the picolinium units in the solid state. Dynamic (1)H NMR spectroscopy is employed to probe in solution the relative energy barriers for rotations by the phenylene and pyridinium rings in the tetracationic cyclophane component of the [2]catenanes. Where there are co-conformational changes that are stereochemically "allowed", crown ether circumrotation and rocking processes are also investigated for the relative rates of their occurrence. The outcome is one whereby the three [2]catenanes containing BPP34C10, 1/5NPPP36C10, and 1/5DNP38C10 exist as one major enantiomeric pair of diastereoisomers amongst two, four, and eight diastereoisomeric pairs of enantiomers, respectively. The diastereoisomerism is a consequence of the presence of axial chirality together with helical and/or planar chirality in the same interlocked molecule. These [2]catenanes constitute a rich reserve of new stereochemical types that might be tapped for their switching and mechanical properties.     

Synthesis of 2'-O-[2-[(N,N-dimethylamino)oxy]ethyl] modified nucleosides and oligonucleotides.

A versatile synthetic route has been developed for the synthesis of 2'-O-[2-[(N,N-dimethylamino)oxy]ethyl] (abbreviated as 2'-O-DMAOE) modified purine and pyrimidine nucleosides and their corresponding nucleoside phosphoramidites and solid supports. To synthesize 2'-O-DMAOE purine nucleosides, the key intermediate B (Scheme 1) was obtained from the 2'-O-allyl purine nucleosides (13a and 15) via oxidative cleavage of the carbon-carbon bond to the corresponding aldehydes followed by reduction. To synthesize pyrimidine nucleosides, opening the 2,2'-anhydro-5-methyluridine 5 with the borate ester of ethylene glycol gave the key intermediate B. The 2'-O-(2-hydroxyethyl) nucleosides were converted, in excellent yield, by a regioselective Mitsunobu reaction, to the corresponding 2'-O-[2-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]ethyl] nucleosides (18, 19, and 20). These compounds were subsequently deprotected and converted into the 2'-O-[2-[(methyleneamino)oxy]ethyl] derivatives (22, 23, and 24). Reduction and a second reductive amination with formaldehyde yielded the corresponding 2'-O-[2-[(N,N-dimethylamino)oxy]ethyl] nucleosides (25, 26, and 27). These nucleosides were converted to their 3'-O-phosphoramidites and controlled-pore glass solid supports in excellent overall yield. Using these monomers, modified oligonucleotides containing pyrimidine and purine bases were synthesized with phosphodiester, phosphorothioate, and both linkages (phosphorothioate and phosphodiester) present in the same oligonucleotide as a chimera in high yields. The oligonucleotides were characterized by HPLC, capillary gel electrophoresis, and ESMS. The effect of this modification on the affinity of the oligonucleotides for complementary RNA and on nuclease stability was evaluated. The 2'-O-DMAOE modification enhanced the binding affinity of the oligonucleotides for the complementary RNA (and not for DNA). The modified oligonucleotides that possessed the phosphodiester backbone demonstrated excellent resistance to nuclease with t(1/2) > 24 h.     

An efficient approach towards the convergent synthesis of "fully-carbohydrate" mannodendrimers

Glycosylation of sugar trityl ethers with sugar 1,2-O-(1-cyano)ethylidene derivatives (the trityl-cyanoethylidene condensation) has been applied to the synthesis of highly branched (dendritic) mannooligosaccharides incorporating a Manalpha1-->3(Manalpha1-->6)Man structural motif. The convergent synthetic strategy used to assemble these oligosaccharides was based on the use of glycosyl acceptors and/or a glycosyl donor already bearing this structural motif. The former were represented by mono- and ditrityl ethers of ManalphaOMe, Manalpha1-->3ManalphaOMe, and Manalpha1-->3(Manalpha1-->6)ManalphaX, where X=OMe or SEt. The pivotal glycosyl donor was the peracetylated 1,2-O-(1-cyano)ethylidene-3,6-di-O-(alpha-D-mannopyranosyl)-beta-D-mannopyranose (1), prepared by orthogonal Helferich glycosylation of the known 1,2-O-(1-cyano)ethylidene-beta-D-mannopyranose with tetra-O-acetyl-alpha-D-mannopyranosyl bromide followed by O-acetylation. Glycosylation of acetates of methyl 6-O-trityl-alpha-D-mannopyranoside and methyl 3,6-di-O-trityl-alpha-D-mannopyranoside with one equivalent of the donor 1 gave rise to the isomeric tetrasaccharide derivatives, Manalpha1-->3(Manalpha1-->6)Manalpha1-->6ManalphaOMe and Manalpha1-->3(Manalpha1-->6)Manalpha1-->3ManalphaOMe, respectively. The latter derivative was further mannosylated at the remaining 6-O-trityl acceptor site to give the protected pentasaccharide Manalpha1-->3(Manalpha1-->6)Manalpha1-->3(Manalpha1-->6)ManalphaOMe. The isomeric pentasaccharide, Manalpha1-->3(Manalpha1-->6)Manalpha1-->6(Manalpha1-->3)ManalphaOMe, was prepared by reaction of 1 with the 6-O-trityl derivative of (Manalpha1-->3)ManalphaOMe. In a similar fashion, 6'- and 6"-O-trityl derivatives of the branched trisaccharide Manalpha1-->3(Manalpha1-->6)ManalphaOMe served as precursors for two isomeric mannohexaosides. The 3,6-di-O-trityl ether of ManalphaOMe and the 6',6"-di-O-trityl ether of Manalpha1-->3(Manalpha1-->6)ManalphaX (X=OMe or SEt) were efficiently bis-glycosylated with the donor 1 to give the corresponding protected mannoheptaoside and mannononaoside. The yields of these glycosylations with the donor 1 ranged from 50 to 66 %. Final deprotection of all the oligosaccharides was straightforward and afforded the target products in high yields. Both the acylated and deprotected products were characterized, and the intersaccharide connectivities were elucidated by extensive one- and two-dimensional NMR spectroscopy. The described blockwise convergent approach allows assembly of a variety of 3,6-branched mannooligosaccharides.