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.     

A fluorinated selenide linker for solid-phase synthesis of n-pentenyl glycosides

[reaction: see text] A fluorine-labeled selenide linker for installing terminal isolated olefins has been synthesized in high overall yield. The resin-bound linker could be glycosylated both with glycosyl trichloroacetimidates and glycosyl fluorides. The linker did not decompose after oxidation with tBuOOH but underwent beta-elimination when it was subjected to heat. This allowed the released n-pentenyl glycoside 15 to be isolated in excellent yield and purity after filtration.     

Isocyanide addition to MN2(CO)5(Ph2PCH2PPh2)2 and the formation of a four-electron doubly-bridging isocyanide

The reactions of Fe(CO)₅, Fe(CO)₄P(C₆H₅)₃, M(CO)₆ (M  W, Mo, Cr), and (CH₃C₅H₄Mn(CO)₃ with KH and several boron and aluminium hydrides were investigated. Iron pentacarbonyl was converted quantitatively to K⁺Fe(CO)₄-(CHO) by hydride transfer from KBH(OCH₃)₃ allowing isolation of [P(C₆H₅)₃]₂-Nⁿ⁺Fe(CO)₄(CHO)^? in 50% yield. Lower yields were obtained with LiBH(C₂H₅)₃, and other hydride sources gave little or no formyl product. The stability of Fe(CO)₄(CHO)^? in THP was found to depend on the cation, decreasing in the order [P(C₆H₅)₃]₂N⁺ > K⁺ > Na⁺ > Li⁺. No formyl complexes were isolated and no spectroscopic evidence for formyl formation was observed in the reactions of the other transition metal carbonyls with several hydride sources. Fe(CO)₄-P(C₆H₅)₃ gave K₂Fe(CO)₄ when treated with KHB(OCH₃)₃. When treated with LiBH(C₂H₅)₃, W(CO)₆ gave a mixture of HW₂(CO)₁₀^?and (OC)₅W(COC₂H₅)^?; the latter was methylated to give the carbene complex (OC)₅WC(OCH₃)C₂H₅.     

Anionic carbonyl complexes of the group VI transition metals with sulfur containing ligands

Anionic complexes of the type [M(CO)₄(dpet)]^? (where M is Cr, Mo or W and dpet is the anion of 2-(diphenylphosphino)ethanthiol) are readily prepared by the reaction of the Tl(dpet) and [M(CO)₅X]^? anions (X = halogen). These complex anions appear to have the normal octahedral geometry with the dpet ligand coordinated through both the P and S atoms. When treated with methyl or allyl halides, neutral complexes of the type M(CO)₄(dpet—R) are formed (where R is an allyl or methyl group now bound to the sulfur atom). By treating Tl^I salts of o-aminothiophenol (atp), o-methylmercaptophenol (nmp) and methylxanthic acid (mxt), with [M(CO)₅]^? anions, the respective complexes [M(CO)₄(atp)]^?, [M(CO)₄(mmp)]^? and [M(CO)₅(mxt)]^? are formed.     

A novel way to study the initial stages of soap-free emulsion polymerizations: The intercalation of polystyrene oligomers into hydrotalcite

The dominant species in the early stages of an emulsifier-free emulsion polymerization of styrene has been found to be an oligomer of two to three monomer units using a novel trapping technique. This involved the intercalation of charged primary oligomers between the layers of a hydrotalcite, [Mg₄Al₂(OH)₁₂]²⁺[A]^2- (where A = dianion). Hydrotalcites are an important class of lamellar, inorganic compounds whose interlayer spacing can be mod-ified by anion exchange. Our approach first involved preparing a hydrotalcite precursor in which the layers were propped apart by an organic dianion (terephthalate = TA). This material was then used to capture the negatively charged polystyrene oligomers from the emulsion polymerization reaction mixture. We found that TA was rapidly ion-exchanged for the charged oligomers. The resulting pillared hydrotalcite material was characterized using XRD and SEC. We found that the interlayer spacing between the hydroxide layers increased to 23.2 Å on exposure to the emulsion reaction mixture. This represents an interlayer expansion of 18.3 Å (after subtraction of the hydroxide layer contribution), which is cnsistent with intercalation of oligomers with two to three monomer units arranged in a bilayer. This size estimate was confirmed by the results of size exclusion chromatography. © 1995 John Wiley & Sons, Inc.     

Control of lysine reactivity in four-helix bundle proteins by site-selective pKa depression: expanding the versatility of proteins by postsynthetic functionalization

Five 42-residue polypeptides have been designed to fold into hairpin helix-loop-helix motifs that dimerize to form four-helix bundles, and to serve as protein scaffolds for the elucidation at the molecular level of the principles that control and fine-tune lysine and ornithine reactivities in a protein context. Site-selective control of Lys and Orn reactivity provides a mechanism for addressing directly individual residues and is a prerequisite for the site-selective functionalization of folded proteins. Several lysine and one ornithine residues were introduced on the surface and in the hydrophobic core of the folded motif. The reactivity of each residue was determined by measuring the degree of acylation of the trypsin cleaved fragments by HPLC and mass spectrometry. The most reactive residues were Orn34 and Lys19, both of which were located in d positions in the heptad repeat, and therefore in hydrophobic environments. Upon reaction of the helix-loop-helix dimer KA-I with one equivalent of mono-p-nitrophenyl fumarate, Orn34 was acylated approximately three times more efficiently than Lys19, whereas Lys10 (b position), Lys15 (g position), and Lys33 (c position) remained unmodified. In the sequence KA-I-A(15) Lys15 was replaced by an alanine residue and the selectivity of Orn34 over Lys19 increased to approximately a factor of six, probably because Lys15 had the capacity to reduce the pK(a) value of Lys19 and 85 % of site-selectively monoacylated product was obtained. The pH dependence of the acylation reaction was determined and showed that the pK(a) of the reactive residues were 9.3, more than a pK(a) unit below the magnitude of the corresponding residue in a solvent exposed position. Introducing Lys and Orn residues into a or d positions of the heptad repeat therefore serves as a mechanism of depressing their pK(a) to increase their reactivity site selectively. Extensive NMR and CD spectroscopic analyses showed that the sequences fold according to prediction.     

Phenylated polyimides via bifunctional monomers

The synthesis of two phenylated bifunctional monomers, dimethyl 4-(4-(p-aminophenoxy)phenyl)-3,5,6-triphenylphthalate and dimethyl 4-(4-(4-(p-aminophenoxy)phenoxy)phenyl)-3,5,6-triphenylphthlate, was accomplished. Polymerization in solution or by a bulk polymerization procedure yielded a series of low molecular weight phenylated polyimides. The polymers were soluble in chlorinated hydrocarbons and exhibited thermal stabilities comparable to other polyimide systems.     

Übergangsmetall—methylen-komplexe : XXXI. Primärkomplexierung von diazoalkanen an metall—metall-mehrfachbindungen; ein weiterer koordinationstyp

An unexpected novel coordination mode of diazoalkanes has been verified via addition of 2-diazopropane to the metal—metal triple bond of bis[dicarbonyl(η⁵-pentamethylcyclopentadienyl)molybdenum] (MoMo). The dinuclear 1:1 addition product isolated in nearly quantitative yield is structurally characterized by a bent, 4-electron type η¹:η²-diazoalkane ligand, with the terminal nitrogen atom symmetrically bridging the metal-metal “single bond” (d(MoMo) 305.0(2) pm; d(Mo---N(1)) 212.0(12) and 212.6(10) pm, respectively) and the second nitrogen atom being bonded to one molybdenum atom only (d(Mo---N(2)) 213.4(13) pm).     

Exo-metal coordination by a tricyclic [(P(mu-N-2-NC5H4))2(mu-O)]2 dimer in [(P(mu-N-2-NC5H4))2(mu-O)]2(CuCl x (C5H5N)2)4 (2-NC5H4 = 2-pyridyl, C5H5N = pyridine)

The in situ reaction of the phosphazane dimer [CIP(mu-N-2-NC5H4)]2 (2) with CuCl in the presence of CsH5N/H2O gives the title complex [(P(mu-N-2-NC5H4))2(mu-O)]2(CuCl x (C5H5N)2)4 (1), containing a tricyclic [(P(mu-N-2-NC5H4))2(mu-O)]2 ligand which is isoelectronic with species of the type [(P(mu-NR))2NR]2.