Conformational analysis of dipeptide‐derived polyisocyanides

The conformational properties of polymers derived from isocyanodipeptides have been investigated with a combination of model calculations, X‐ray diffraction, and circular dichroism spectroscopy. Depending on the configuration of the side chains, defined arrays of hydrogen bonds along the polymeric backbone are formed. This leads to a well‐defined conformation as, for example, expressed in the formation of lyotropic liquid‐crystalline phases and increased helical stability. Upon the disruption of the hydrogen bonds by a strong acid, a less well‐defined macromolecular conformation is observed. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1725–1736, 2003     

Multi-point Taylor expansions of analytic functions

Taylor expansions of analytic functions are considered with respect to several points, allowing confluence of any of them. Cauchy-type formulas are given for coefficients and remainders in the expansions, and the regions of convergence are indicated. It is explained how these expansions can be used in deriving uniform asymptotic expansions of integrals. The method is also used for obtaining Laurent expansions in several points as well as Taylor-Laurent expansions.

     

A supramolecular hydrogen‐bonded complex between 1,3,5‐tris(diisobutylhydroxysilyl)benzene and trans‐bis(4‐pyridyl)ethylene

The trisilanol 1,3,5‐(HOi‐Bu₂Si)₃C₆H₃ ( 7 ), prepared in three steps from 1,3,5‐tribromobenzene via the intermediates 1,3,5‐(Hi‐Bu₂Si)₃C₆H₃ ( 8 ) and 1,3,5‐(Cli‐Bu₂Si)₃C₆H₃ ( 9 ) forms an equimolar complex with trans‐bis(4‐pyridyl)ethylene (bpe), 7 ·bpe, whose structure was investigated by X‐ray crystallography. The hydrogen‐bonded network features a number of SiO? H(H)Si and SiO? H hydrogen bridges. Evidence was found for cooperative strengthening within the sequential hydrogen bonds. Copyright © 2007 John Wiley & Sons, Ltd.     

Evidence for Interchange Ligand‐Exchange Processes on Solvated Beryllium Cations

The ligand‐exchange mechanism of solvated Be²⁺ cations has been studied by means of DFT calculations (RB3LYP/6‐311+G**). Ligand exchange around [BeL₄]²⁺, where L=H₂O, NH₃, CO₂, formaldehyde (H₂CO), HCN, N₂, and CO, was found to follow an associative interchange (I_a) process in all cases. The size of the activation barrier is almost independent of the type of donor atom, and depends mainly on the hybridization undergone by the donor atom. This, in turn, suggests that steric effects play a major role in solvent‐ and ligand‐exchange reactions in Be²⁺ systems.     

Identification of extracellular nanoparticle subsets by nuclear magnetic resonance

Exosomes are a subset of secreted lipid envelope-encapsulated extracellular vesicles (EVs) of 50–150 nm diameter that can transfer cargo from donor to acceptor cells. In the current purification protocols of exosomes, many smaller and larger nanoparticles such as lipoproteins, exomers and microvesicles are typically co-isolated as well. Particle size distribution is one important characteristics of EV samples, as it reflects the cellular origin of EVs and the purity of the isolation. However, most of the physicochemical analytical methods today cannot illustrate the smallest exosomes and other small particles like the exomers. Here, we demonstrate that diffusion ordered spectroscopy (DOSY) nuclear magnetic resonance (NMR) method enables the determination of a very broad distribution of extracellular nanoparticles, ranging from 1 to 500 nm. The range covers sizes of all particles included in EV samples after isolation. The method is non-invasive, as it does not require any labelling or other chemical modification. We investigated EVs secreted from milk as well as embryonic kidney and renal carcinoma cells. Western blot analysis and immuno-electron microscopy confirmed expression of exosomal markers such as ALIX, TSG101, CD81, CD9, and CD63 in the EV samples. In addition to the larger particles observed by nanoparticle tracking analysis (NTA) in the range of 70–500 nm, the DOSY distributions include a significant number of smaller particles in the range of 10–70 nm, which are visible also in transmission electron microscopy images but invisible in NTA. Furthermore, we demonstrate that hyperpolarized chemical exchange saturation transfer (Hyper-CEST) with ¹²⁹Xe NMR indicates also the existence of smaller and larger nanoparticles in the EV samples, providing also additional support for DOSY results. The method implies also that the Xe exchange is significantly faster in the EV pool than in the lipoprotein/exomer pool.

Diffusion and xenon NMR based methods to determine a very broad range of sizes and sub-sets of extracellular vesicles.     

Synthesis and characterization of Cu,Ni and Zn binding capability of some amino- and imidazole hydroxamic acids: Effects of substitution of side chain amino-N for imidazole-N or hydroxamic-N-H for -N-CH3 on metal complexation

Solution equilibrium studies on Cu(II)-, Ni(II)- and Zn(II)-N-Me-β-Alaninehydroxamic acid (N-Me-β-Alaha), -N-Me-α-alaninehydroxamic acid (N-Me-α-Alaha), -Imidazole-4-carbohydroxamic acid (Im-4-Cha), -N-Me-imidazole-4-carbohydroxamic acid (N-Me-Im-4-Cha) and -Imidazole-4-acetohydroxamic acid (Im-4-Aha) systems have been performed by pH-potentiometry, UV–Vis spectrophotometry, EPR, CD, ESI-MS and ¹H NMR methods. According to the results: (i) the amino-N atoms are more basic in N-Me-α-Alaha and N-Me-β-Alaha than the hydroxamate function, but the trend is just the opposite between the imidazole-N(3) and hydroxamate. (ii) The metal ion anchor is always the hydroxamate part in the amino acid derivatives, while it is always the imidazole-N(3) in the studied imidazolehydroxamic acids. (iii) The three studied N-Me derivatives do not form metallacrowns. Only hydroxamate type chelate is formed with N-Me-β-Alaha, but with N-Me-α-Alaha a new type of coordination mode (via amino-N and hydroxamate-O) also exists. N-Me-Im-4-Cha also forms a dinuclear complex, [M₂L₃], with Cu(II) and Ni(II) (but not with Zn(II)). In this complex, one of the three ligands might bridge the two metal ions (five-membered hydroxamate-(O,O) plus five-membered (N_im, O_carb) bridging bis-chelating mode), while each of the additional two ligands binds to one metal. (iv) The two studied N–H derivatives, having dissociable proton on the hydroxamic-N, are able to form metallacrown species. A pentanuclear complex, [M₅L₄H₋₄], is exclusively formed above pH 4 between Cu(II) and Im-4-Aha. Interestingly, this 12-metallacrown-4 type complex, although together with various mononuclear binding isomers, appears also with Ni(II) and Zn(II). Unfortunately, the complexes of Im-4-Cha are not soluble in water at physiological pH at all.     

Study of metal-loaded activated charcoals for the separation and determination of selenium species by energy dispersive X-ray fluorescence analysis

Conversion of adsorption properties of activated charcoal (C^∗) by metal modification towards selenite, selenate and seleno-dl-methionine (Se-Met) was studied. Several metals were included in modification studies and also a procedure was developed for the separation and independent determination of microgram quantities of these selenium species in aqueous solution. Selenium species were collected one by one from the same sample solution onto collector material by adsorbing them directly or after complex formation onto different metal-loaded activated charcoals (MgC^∗ and FeC^∗). The mass of selenium in these collectors was measured directly by energy dispersive X-ray fluorescence spectrometry (EDXRF). Detection limits for all three selenium species were better than 6 μg corresponding to concentration of 60 μg/l with 0.100 l of initial sample volume.     

S1P1-selective in vivo-active agonists from high-throughput screening: off-the-shelf chemical probes of receptor interactions, signaling, and fate

The essential role of the sphingosine 1-phosphate (S1P) receptor S1P(1) in regulating lymphocyte trafficking was demonstrated with the S1P(1)-selective nanomolar agonist, SEW2871. Despite its lack of charged headgroup, the tetraaromatic compound SEW2871 binds and activates S1P(1) through a combination of hydrophobic and ion-dipole interactions. Both S1P and SEW2871 activated ERK, Akt, and Rac signaling pathways and induced S1P(1) internalization and recycling, unlike FTY720-phosphate, which induces receptor degradation. Agonism with receptor recycling is sufficient for alteration of lymphocyte trafficking by S1P and SEW2871. S1P(1) modeling and mutagenesis studies revealed that residues binding the S1P headgroup are required for kinase activation by both S1P and SEW2871. Therefore, SEW2871 recapitulates the action of S1P in all the signaling pathways examined and overlaps in interactions with key headgroup binding receptor residues, presumably replacing salt-bridge interactions with ion-dipole interactions.