How preparation and modification parameters affect PB‐PEO polymersome properties in aqueous solution

The effect of formation and modification methods on the physical properties of polymersomes is critical for their use in applications relying on their ability to mimic functional properties of biological membranes. In this study, we compared two formation methods for polymersomes made from polybutadiene‐polyethylene oxide diblock copolymers: detergent‐mediated film rehydration (DFR) and solvent evaporation (SE). DFR‐prepared polymersomes showed a three times higher permeability compared to SE‐prepared polymersomes as revealed by stopped‐flow light scattering. SE‐prepared polymersomes broke down faster to structures <50 nm diameter when processed with extrusion, which was more pronounced at 5 mg mL^?1, compared to 10, 20, and 25 mg mL^?1. Our results indicate that the bilayer of SE‐prepared polymersomes has a lower apparent fluidity. We also investigated the role of n‐octyl‐β‐d ‐glucopyranoside (OG), a detergent typically used for reconstitution of membrane proteins into lipid bilayers. Specifically, we compared dialysis and biobeads for OG removal to investigate the influence of these methods on bilayer conformation and polymer rearrangement following detergent removal. There was no significant difference found between method, temperature, or time within each method. Our findings provide insight on how biocompatible polymersome production affects the physical properties of the resulting polymersomes. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1581–1592     

Local-in-time adjoint-based method for design optimization of unsteady flows

We present a new local-in-time discrete adjoint-based methodology for solving design optimization problems arising in unsteady aerodynamic applications. The new methodology circumvents storage requirements associated with the straightforward implementation of a global adjoint-based optimization method that stores the entire flow solution history for all time levels. This storage cost may quickly become prohibitive for large-scale applications. The key idea of the local-in-time method is to divide the entire time interval into several subintervals and to approximate the solution of the unsteady adjoint equations and the sensitivity derivative as a combination of the corresponding local quantities computed on each time subinterval. Since each subinterval contains relatively few time levels, the storage cost of the local-in-time method is much lower than that of the global methods, thus making the time-dependent adjoint optimization feasible for practical applications. Another attractive feature of the new technique is that the converged solution obtained with the local-in-time method is a local extremum of the original optimization problem. The new method carries no computational overhead as compared with the global implementation of adjoint-based methods. The paper presents a detailed comparison of the global- and local-in-time adjoint-based methods for design optimization problems governed by the unsteady compressible 2-D Euler equations.     

Side Products in Nucleotide Chemistry

Abstract

Alkyl bisaminophosphorodiamidites¹ (1) has been shown to be versatile reagents for in situ preparation of d-nucleoside-3-phosphoramidites^2,3,4 (2.)     

SYNTHESIS OF SOME NEW 4-AMINO-1,2,4-TRIAZOLE DERIVATIVES AS POTENTIAL ANTI-HIV AND ANTI-HBV

Some novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazolylisoindole-1,3-dione 2a–c were prepared by heating 4-amino-5-aryl-1,2,4-triazole-3-thiones 1a–c with different (1,3-dioxo-1,3-dihydro-isoindol-2-yl) carboxylic acids in POCl₃. Compounds 2a, b were hydrolyzed using HCl to yield [1,2,4]triazolo[3,4-b][1,3,4]thiadiazolyl-alkylamines 3a, b. Coupling 1a, c with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (ABG) afforded the corresponding S-glucosides 4a, b, which on oxidation with KMnO₄ gave the corresponding sulfone 5. Treatment 1b, c with diphenyl diazomethane afforded benzhydrylsulfanyltriazolylamines 7a, b. 1,8-Bis-(4-chloro-phenyl)-bis[1,2,4]triazolo[3,4-c-,4′,3′-e][1,2,4,5]dithiadiazine 8 was formed by oxidation of 1b with lead tetracetate. Compound 1c reacted with morpholine in the presence of KI and I₂ to give the triazolodisulfide ⁹ El-Barbary, A. A., Fahmy, M., El-Badawi, M., El-Brembaly, K. and El-Brollosi, N. R. 1991. Rev. Roum. Chim., 36(619) [Google Scholar].     

CHIROPTICAL PROPERTIES OF 1-DEOXY-1-THIOGALACTOPYRANOSIDES

Abstract

Continuing our studies of optically active sulfides we have investigated flexible systems incorporating the 1.3-O,S-chromophore, e.q., alkyl α-and B-D-thiogalactopyranosides and their tetraacetates. Although most substances were known from the literature, constitutional, configurational, and conformational assignments had hardly ever been proved rigorously; we therefore had to provide a firm basis by a systematic analysis of the ¹H and ¹³C NMR spectra of thioglycosides, the complexity of the carbohydrate signals necessitating high field studies. The compounds were thus, in the end, correlated with the natural thiogalactoside lincomycin, whose structure including its absolute configuration is known from X-ray investigations. CD curves have been measured at various temperatures in the range of 185–300 nm on a commercial spectropolarimeter equipped with a data processor and connected to a table calculator and plotter, directly furnishing data suitable for, e.g., Kronig-Kramers type transformations or curve analysis and displaying the results. These CD data were correlated with the UV spectra and the ORD curves of the substrates. Typically, the UV curves are devoid of detail except in the case of the acetates, where a shoulder in the region of the n→π? transition is discernible. In the ORD, the Cotton effects (CE) are largely suppressed by the background contribution of the “invisible giant” in the far UV. In the thiogalactopyranosides all accessible Cotton effects are associated with electron transitions within the sulfur or possibly the coupled O-C-S chromophore, whereas a relatively small negative, composite CE is contributed by the acetate carbonyl groups in the acetates.     

Mono‐ and Bis(pyrrolo)tetrathiafulvalene Derivatives Tethered to C60: Synthesis,Photophysical Studies,and Self‐Assembled Monolayers

A series of mono‐ (MPTTF) and bis(pyrrolo)tetrathiafulvalene (BPTTF) derivatives tethered to one or two C₆₀ moieties was synthesized and characterized. The synthetic strategy for these dumbbell‐shaped compounds was based on a 1,3‐dipolar cycloaddition reaction between aldehyde‐functionalized MPTTF/BPTTF derivatives, two different tailor‐made amino acids, and C₆₀. Electronic communication between the MPTTF/BPTTF units and the C₆₀ moieties was studied by a variety of techniques including cyclic voltammetry and absorption spectroscopy. These solution‐based studies indicated no observable electronic communication between the MPTTF/BPTTF units and the C₆₀ moieties. In addition, femtosecond and nanosecond transient absorption spectroscopy revealed, rather surprisingly, that no charge transfer from the MPTTF/BPTTF units to the C₆₀ moieties takes place on excitation of the fullerene moiety. Finally, it was shown that the MPTTF–C₆₀ and C₆₀–BPTTF‐C₆₀ dyad and triad molecules formed self‐assembled monolayers on a Au(111) surface by anchoring to C₆₀.     

Synthesis of Oxacyclic Scaffolds via Dual Ruthenium Hydride/Brønsted Acid‐Catalyzed Isomerization/Cyclization of Allylic Ethers

A ruthenium hydride/Brønsted acid‐catalyzed tandem sequence is reported for the synthesis of 1,3,4,9‐tetrahydropyrano[3,4‐b]indoles (THPIs) and related oxacyclic scaffolds. The process was designed on the premise that readily available allylic ethers would undergo sequential isomerization, first to enol ethers (Ru catalysis), then to oxocarbenium ions (Brønsted acid catalysis) amenable to endo cyclization with tethered nucleophiles. This methodology provides not only an attractive alternative to the traditional oxa‐Pictet–Spengler reaction for the synthesis of THPIs, but also convenient access to THPI congeners and other important oxacycles such as acetals.     

Synthesis of a Natural Product‐Like Compound Collection through Oxidative Cleavage and Cyclization of Linear Peptides

Massive efforts in molecular library synthesis have strived for the development of synthesis methodology which systematically delivers natural product‐like compounds of high spatial complexity. Herein, we present a conceptually simple approach that builds on the power of solid‐phase peptide synthesis to assemble precursor peptides (oligomers) designed to undergo oxidative cascade reactions. By harnessing the structural side‐chain diversity and inherent stereochemical features offered by readily available amino acids (monomers), a proof‐of‐concept collection of 54 skeletally and stereochemically diverse compounds was generated, and selected compounds were elaborated into isoform‐selective metalloprotease inhibitors.     

ZIBgridfree: efficient conformational analysis by partition-of-unity coupling

Obtaining a sufficient sampling of conformational space is a common problem in molecular simulation. We present the implementation of an umbrella-like adaptive sampling approach based on function-based meshless discretization of conformational space that is compatible with state of the art molecular dynamics code and that integrates an eigenvector-based clustering approach for conformational analysis and the computation of inter-conformational transition rates. The approach is applied to three example systems, namely $n$ -pentane, alanine dipeptide, and a small synthetic host-guest system, the latter two including explicitly modeled solvent.     

Hot Branching Dynamics in a Light‐Harvesting Iron Carbene Complex Revealed by Ultrafast X‐ray Emission Spectroscopy

Iron N‐heterocyclic carbene (NHC) complexes have received a great deal of attention recently because of their growing potential as light sensitizers or photocatalysts. We present a sub‐ps X‐ray spectroscopy study of an Fe^IINHC complex that identifies and quantifies the states involved in the deactivation cascade after light absorption. Excited molecules relax back to the ground state along two pathways: After population of a hot ³MLCT state, from the initially excited ¹MLCT state, 30 % of the molecules undergo ultrafast (150 fs) relaxation to the ³MC state, in competition with vibrational relaxation and cooling to the relaxed ³MLCT state. The relaxed ³MLCT state then decays much more slowly (7.6 ps) to the ³MC state. The ³MC state is rapidly (2.2 ps) deactivated to the ground state. The ⁵MC state is not involved in the deactivation pathway. The ultrafast partial deactivation of the ³MLCT state constitutes a loss channel from the point of view of photochemical efficiency and highlights the necessity to screen transition‐metal complexes for similar ultrafast decays to optimize photochemical performance.