Internal structure of a thin film of mixed polymeric micelles on a solid/liquid interface

The adsorption of mixed micelles of poly(4-(2-amino hydrochloride-ethylthio)-butylene)- block-poly(ethylene oxide), PAETB 49- b-PEO 212 and poly(4-(2-sodium carboxylate-ethylthio)-butylene)- block-poly(ethylene oxide), PCETB 47- b-PEO 212 on solid/liquid interfaces has been studied with light, X-ray, and neutron reflectometry. The structure of the adsorbed layer can be described with a two-layer model consisting of an inner layer formed by the coacervate of the polyelectrolyte blocks PAETB 49 and PCETB 47 ( approximately 1 nm) and an outer layer of PEO 212 blocks ( approximately 6 nm). The micelles unfold upon adsorption forming a rather homogeneous flat layer that exposes its polyethylene oxide chains into the solution, thus rendering the surface antifouling after modification with the micelles.     

Stable ion and electrophilic chemistry of the sterically crowded stilbene 1,1'-Bi(benzocyclobutenylidene) and its derivatives

Generation and NMR studies of novel carbocations and carboxonium ions are reported from sterically hindered stilbene 1,1'-bi(benzocyclobutenylidene) 1, its dimethoxy derivative 5, and from their skeletally rearranged derivatives, namely, the spirocyclic ketone 6, diastereomeric alcohols 7 and isomeric diols 8. Quenching experiments on the carbocations under various conditions resulted in the formation/isolation of several novel covalent adducts. Acid-catalyzed isomerization of the diols 8 produced a remarkable dimeric molecule, whose structure was confirmed by X-ray analysis. Reactions of hindered stilbenes 1 and 5 with Br 2/CDCl 3 were examined via NMR experiments. The experimentally observed carbocations were also studied computationally by GIAO-DFT and by NICS.     

Enantiotopos-differentiating (-)-sparteine-mediated gamma-deprotonation of 1-alkenyl carbamates: DFT calculations verify the observed stereoselectivity

The enantioselective lithiation/gamma-deprotonation of three 1-alkenyl N,N-diisopropylcarbamates 6 by alkyllithium/(-)-sparteine has been modeled by the DFT method B3LYP/6-31G(d). The results of these calculations predict the preferential removal of the gamma-pro-R proton from the precomplexes 7 to give the (S)-lithio derivates 8. The calculations also indicate the necessity of an anion-stabilizing substituent (Ph, -CC-Ph) in the alpha-position of the substrate. These data are in excellent concordance with the experimental results. It is demonstrated that the formation and the properties of lithium carbanions are predictable with high accuracy by standard quantum chemical calculations if these species are monomeric and rigidified to some extent by chelation.     

Hydrophilic alcohol ethoxylates as efficiency boosters for microemulsions

Highly amphiphilic polyalkane-PEO diblock copolymers drastically increase the solubilization capacity of surfactants in microemulsions if they are used in small quantities as additive to the surfactant. This effect goes along with an additional reduction of the already very low interfacial tension between water and oil. Lamellar phases, which usually develop when the surfactant becomes more efficient, are suppressed to a large extent. In this work we use another type of additive, namely hydrophilic alcohol ethoxylates. These amphiphiles are identical with the previously used block copolymers with respect to the hydrophilic moiety. However, they contain only small hydrocarbon groups ranging from C8 to C18. A typical example from the hydrophilic alcohol ethoxylates is C12E100. Both additive types increase surfactant efficiency equally with respect to mass fraction in the mixture. Because the alcohol ethoxylate additives decorate the surfactant film only on the aqueous side, they influence the curvature of the surfactant membrane or, in other words, the temperature behavior of the microemulsion. Together with nonionic surfactants, however, the shift of the one-phase region to higher temperatures is only a few degrees Celsius. Just as with the polyalkane-PEO block copolymers, the hydrophilic alcohol ethoxylates suppress lamellar phases. This behavior is especially pronounced if the hydrophobic groups are small or the PEO chains are long. We found that hydrophobic units as short as C 8 are sufficient to largely anchor the PEO chains at the interface. If C12 or C18 hydrocarbon unit are used instead, the PEO chains are fully interfacially active, even if the hydrophilic chain contains up to about 500 EO units. We applied the new additives in bicontinuous and in droplet microemulsions and used nonionic, as well as ionic, surfactants, namely C10E4 and AOT. In contrast to polyalkane-PEO blockcopolymers the new additives are easy to synthesize and are commercially available. Therefore, they might be interesting in applications.     

Artificial chemokines: combining chemistry and molecular biology for the elucidation of interleukin-8 functionality

How can we understand the contribution of individual parts or segments to complex structures? A typical strategy to answer this question is simulation of a segmental replacement followed by realization and investigation of the resulting effect in structure-activity studies. For proteins, this problem is commonly addressed by site-directed mutagenesis. A more general approach represents the exchange of whole secondary structure elements by rationally designed segments. For a demonstration of this possibility we identified the alpha-helix at the C-terminus of human interleukin-8 (hIL-8). Since this chemokine possesses four conserved cysteine residues, it can easily be altered by ligation strategies. A set of different segments, which are able to form amphiphilic helices, was synthesized to mimic the C-terminal alpha-helix. Beside sequences of alpha-amino acids, oligomers of non-natural beta(3)-amino acids with the side chains of canonical amino acids were introduced. Such beta-peptides form helices, which differ from the alpha-helix in handedness and dipole orientation. Variants of the semisynthetic hIL-8 proteins demonstrated clearly that the exact side chain orientation is of more importance than helix handedness and dipole orientation. The activity of a chimeric protein with a beta-peptide helix that mimics the side chain orientation of the native alpha-helix most perfectly is comparable to that of the native hIL-8. Concepts like this could be a first step toward the synthesis of proteins consisting of large artificial secondary structure elements.     

Reusable optical bioassay platform with permeability-controlled hydrogel pads for selective saccharide detection

A reusable optical bioassay platform using permeability-controlled hydrogel pads for selective saccharide detection has been developed. An optical glucose detection assay based on fluorescence resonance energy transfer (FRET) between dye-labeled dextran and Concanavalin A (ConA) was incorporated into hydrogel pads by entrapment. The hydrogel pads are constructed from hemispherical hydrogel attached onto hydrophobic surfaces of a microtiter plate. The resulted hemispherical hydrogel pads entrapping the sensing biological materials were further surface coated with polyelectrolyte multilayers through a Layer-by-Layer (LbL) self-assembly process to create a permeability-controlled membrane with nanometer thickness. The selective permeable LbL film deposited on the hydrogel surface allows small molecular weight analytes to diffuse into the hydrogel pads while the large molecular weight sensing biological molecules are immobilized. An encapsulation efficiency of 75% for the ConA/Dextran complex within the coated hydrogel pads was achieved and no significant leakage of the complex was observed. Glucose calibration curve with linear range from 0 to 10 mM glucose was obtained. Selective permeability of the hydrogel pads has been demonstrated by measurement of saccharides with various molecular weights. The LbL hydrogel pads could selectively detect monosaccharides (glucose, MW = 180) and disaccharides (sucrose, MW = 342) while polysaccharides (dextran, MW ∼ 70 kDa) cannot diffuse through the LbL layer and are excluded. LbL hydrogel pads allow regeneration of the FRET system with good signal reproducibility of more than 90% to construct a reusable and reagentless optical bioassay platform.     

Electrophilic S‐Trifluoromethylation of Cysteine Side Chains in α‐ and β‐Peptides: Isolation of Trifluoro‐methylated Sandostatin® (Octreotide) Derivatives

The new electrophilic trifluoromethylating 1‐(trifluoromethyl)‐benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF₃ groups to the S‐atom of cysteine side chains of α‐ and β‐peptides (up to 13‐residues‐long; products 7 – 14 ). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2‐position). The products are purified by chromatography, and identified by ¹H‐, ¹³C‐, and ¹⁹F‐NMR spectroscopy, by CD spectroscopy, and by high‐resolution mass spectrometry. The CF₃ groups, thus introduced, may be replaced by H (Na/NH₃), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin‐labelling, imaging, PET) are discussed.     

Sandwich-type tetranuclear lanthanide complexes with cucurbit[6]uril: from molecular compounds to coordination polymers

Sandwich-type lanthanide complexes with macrocyclic ligand cucurbit[6]uril (C 36H 36N 24O 12, CB[6]) were synthesized under hydrothermal conditions from aqueous solutions of lanthanide(III) bromides, CB[6], and 4-cyanopyridine. According to X-ray analysis (Ln = La, Pr, Dy, Ho, Er, and Yb), the compounds with different structural types of lanthanide cores have a common fragment where the tetranuclear hydroxo complex is sandwiched between two macrocycles {(IN@CB[6])Ln 4(mu 3-OH) 4(IN@CB[6])} (6+) (IN = isonicotinate). The photoluminescence (for Ln = Eu) and Fourier transform ion cyclotron resonance mass spectra (for Ln = Pr, Dy, and Er) were studied. The compounds are used for the first time as precursors for the synthesis of lanthanide-silver heterometallic coordination polymers. The chainlike crystal structure of polymers (Ln = La, Pr, and Dy) is constituted by the sandwich complexes linked via the coordination of IN nitrogen atoms to the silver atoms.     

Facile Recoding of Selenocysteine in Nature

Selenocysteine (Sec or U) is encoded by UGA, a stop codon reassigned by a Sec‐specific elongation factor and a distinctive RNA structure. To discover possible code variations in extant organisms we analyzed 6.4 trillion base pairs of metagenomic sequences and 24 903 microbial genomes for tRNA^Sec species. As expected, UGA is the predominant Sec codon in use. We also found tRNA^Sec species that recognize the stop codons UAG and UAA, and ten sense codons. Selenoprotein synthesis programmed by UAG in Geodermatophilus and Blastococcus, and by the Cys codon UGU in Aeromonas salmonicida was confirmed by metabolic labeling with ⁷⁵Se or mass spectrometry. Other tRNA^Sec species with different anticodons enabled E. coli to synthesize active formate dehydrogenase H, a selenoenzyme. This illustrates the ease by which the genetic code may evolve new coding schemes, possibly aiding organisms to adapt to changing environments, and show the genetic code is much more flexible than previously thought.