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Two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC/TOF-MS) is superior for chromatographic separation and provides great sensitivity for complex biological fluid analysis in metabolomics. However, GC×GC/TOF-MS data processing is currently limited to vendor software and typically requires several preprocessing steps. In this work, we implement a web-based platform, which we call GC²MS, to facilitate the application of recent advances in GC×GC/TOF-MS, especially for metabolomics studies. The core processing workflow of GC²MS consists of blob/peak detection, baseline correction, and blob alignment. GC²MS treats GC×GC/TOF-MS data as pictures and clusters the pixels as blobs according to the brightness of each pixel to generate a blob table. GC²MS then aligns the blobs of two GC×GC/TOF-MS data sets according to their distance and similarity. The blob distance and similarity are the Euclidean distance of the first and second retention times of two blobs and the Pearson's correlation coefficient of the two mass spectra, respectively. GC²MS also directly corrects the raw data baseline. The analytical performance of GC²MS was evaluated using GC×GC/TOF-MS data sets of Angelica sinensis compounds acquired under different experimental conditions and of human plasma samples. The results show that GC²MS is an easy-to-use tool for detecting peaks and correcting baselines, and GC²MS is able to align GC×GC/TOF-MS data sets acquired under different experimental conditions. GC²MS is freely accessible at http://gc2ms.web.cmdm.tw. [ABSTRACT FROM AUTHOR]

The viability of 1,3-dipolar cycloadditions of a series of 1,3-dipolar molecules (azomethine ylide, ozone, nitrone, nitrile imine, nitrile ylide, nitrile oxide, diazomethane, and methyl azide) onto the sidewalls of carbon nanotubes has been assessed theoretically by means of a two-layered ONIOM approach. The theoretical calculations predict the following: (i) other than the 18-valence-electron azomethine ylide and ozone, the 16-valence-electron nitrile ylide and nitrile imine are the best candidates for experimentalists to try; (ii) upon 1,3-dipolar cycloaddition, a 1,3-diople molecule is di-σ-bonded to a pair of carbon atoms on the sidewall of SWNT, forming a five-membered ring surface species; (iii) the as-formed 1,3-dipole-SWNT bonding is much weaker than that in the products of the molecular 1,3-DC reactions and can be plausibly broken by heating at elevated temperatures; (iv) the sidewalls of the armchair (n,n) SWNTs (n = 5-10) are subject to the 1,3-DCs of ozone and azomethine ylides; (v) both the 1,3-DC reactivity and retro-1,3-DC reactivity are moderately dependent on the diameters of SWNTs, implying the feasibility of making use of the heterogeneous 1,3-DC chemistry to purify and separate SWNTs diameter-specifically. [ABSTRACT FROM AUTHOR]

Studies the density functional theory calculations of the effects of fluorine substitution on the kinetics of cyclopropylcarbinyl radical ring openings. Stereoelectronic influences; Reactivity and regioselectivity of fluorinated radicals; Activation barrier of carbonyl radicals.

The article informs that phage display has proven very useful for the isolation of high-affinity ligands and receptors from large polypeptide libraries. It has the advantages that large libraries can be easily generated by recombinant methods, library members can be amplified for iterative rounds of enrichment, and primary structure can be determined by DNA sequencing. However, in contrast to synthetic peptide libraries, phage displayed libraries are restricted to the common 20 amino acid building blocks, limiting the functional groups and structural motifs that can be explored.

The thermodynamic stability and electronic structure of 40 surfaces of lithium peroxide (Li2O2) and lithium oxide (Li2O) were characterized using first-principles calculations. As these compounds constitute potential discharge products in Li—oxygen batteries, their surface properties are expected to play a key role in understanding electrochemical behavior in these systems. Stable surfaces were identified by comparing 23 distinct Li2O2 surfaces and 17 unique Li2O surfaces; crystallite areal fractions were determined through application of the Wulff construction. Accounting for the oxygen overbinding error in density functional theory results in the identification of several new Li2O2 oxygen-rich {0001} and {1100} terminations that are more stable than those previously reported. Although oxygen-rich facets predominate in Li2O2, in Li2O stoichiometric surfaces are preferred, consistent with prior studies. Surprisingly, surface-state analyses reveal that the stable surfaces of Li2O2 are half-metallic, despite the fact that Li2O2 is a bulk insulator. Surface oxygens in these facets are ferromagnetic with magnetic moments ranging from 0.2 to 0.5 μB. In contrast, the stable surfaces of Li2O are insulating and nonmagnetic. The distinct surface properties of these compounds may explain observations of electrochemical reversibility for systems in which Li2O2 is the discharge product and the irreversibility of systems that discharge to Li2O. Moreover, the presence of conductive surface pathways in Li2O2 could offset capacity limitations expected to arise from limited electron transport through the bulk. [ABSTRACT FROM AUTHOR]

The assembly behavior of aryl/alkyl imidazolium ionic liquid salts in aqueous solution has been investigated. These salts undergo self-assembly into one-dimensional stacks via hydrophobic and π-π interactions upon increasing concentration, which led to a substantial increase in the solution viscosity in water. Addition of the macrocyclic host molecules cucurbit[n]urils (CB[n]) were found to effectively alter the supramolecular assemblies, as evidenced from the dramatic increase (by CB[7]) and decrease (by CB[8]) in solution viscosity and aggregation size in water, on account of the different binding stoichiometries, 1:1 complexation with CB[7] and 2:1 complexation with CB[8]. Furthermore, the aggregate architectures were controllably modified by competitive guests for the CB[n] hosts. This complex supramolecular systems approach has tremendous implications in the fields of molecular sensor design, nonlinear viscosity modification, and controlled release of target molecules from a defined supramolecular scaffold in water. [ABSTRACT FROM AUTHOR]

Hydroboration of three allotropes of carbon, i.e., diamond (100) surface, [60]fullerene, and singlewall carbon nanotubes (SWNTs), with borane (BH[sub 3]) has been explored by means of quantum chemical calculations. The calculations predicted that the hydroboration of C[sub 60] and the C(100)2 × 1 surface occurs readily, whereas the hydroboration of the sidewall of an armchair (5,5) SWNT is thermoneutral with a barrier height of 11.5 kcal/mol. This suggests that sidewall hydroboration, if viable, would be highly reversible on the (5,5) SWNT. The as-hydroborated carbonous materials can be good starting points for further chemical modification and manipulation of these carbonous materials, given the abundant chemistry of organoboranes. [ABSTRACT FROM AUTHOR]

N-Alkylated chitosan (NACS) may improve the blood clotting efficiency of chitosan (CS). To study its blood coagulation capability, a series of NACSs with various carbon chain lengths and degrees of substitution (DS) of alkyl groups were synthesized and characterized by FTIR, NMR, elemental analysis, and X-ray diffraction (XRD). The corresponding NACS nanofiber membranes (NACS-NM) were subsequently fabricated by electronic spinning technique. SEM, XRD, DSC, surface area, porosity, contact angle, blood absorption, and mechanical properties were used to characterize the CS-NM/NACS-NM. Moreover, cytotoxicity, coagulation, activated partial thromboplastin time, plasma prothrombin time, thrombin time, and platelet aggregation tests were performed to evaluate the biocompatibility and blood coagulation properties of NACS-NM. The results showed that NACS-NM was not cytotoxic. NACS-NM with DS of 19.25% for N-hexane CS (CS6b), 17.87% for N-dodecane CS (CS12b), and 8.97% for N-octadecane CS (CS18a) exhibited good blood clotting performance. Moreover, NACS-NMs favored the activation of coagulation factors and platelets. In addition, intracellular Ca2+ was not related to platelet activation. The above results suggested that NACS-NM would be an effective hemostatic agent. [ABSTRACT FROM AUTHOR]

Biopolymer-based supramolecular hydrogels cross-linked by host-guest interactions are usually mechanically weak as shown in "inverted vials" instead of freestanding 3D constructs. Herein, we describe a novel host-guest macromer (HGM) approach for preparation of biopolymer-based freestanding supramolecular hydrogels. Host-guest macromers are formed by molecular self-assembly between adamantane-functionalized hyaluronic acid (ADxHA) guest polymers and monoacrylated β-cyclodextrins (mono-Ac-βCD) host monomers. Supramolecular hydrogels are readily prepared by UV-induced polymerization of the preassembled host-guest macromers. Such hydrogels are soely cross-linked by in situ formed multivalent host-guest nanoclusters and show significantly reinforced mechanical properties yet still retain desirable supramolecular features. They can self-heal and be remolded into freestanding 3D constructs which afford effective protection on the encapsulated stem cells during the compression remolding, making them promising carriers for therapeutic cells that can quickly adapt to and integrate with surrounding tissues of the targeted defects. We demonstrate that such hydrogels not only sustain extended release of encapsulated proteinaceous growth factors (TGF-β1) but also support chondrogenesis of the human mesenchymal stem cells (hMSCs) and promote cartilage regeneration in a rat model. [ABSTRACT FROM AUTHOR]

We describe here the development of site-specific antibody-polymer conjugates (APCs) for the selective delivery of small interference RNAs (siRNAs) to target cells. APCs were synthesized in good yields by conjugating an aminooxy-derivatized cationic block copolymer to an anti-HER2 Fab or full-length IgG by means of genetically encoded p-acetyl phenylalanine (pAcF). The APCs all showed binding affinity comparable to that of HER2 as their native counterparts and no significant cellular cytotoxicity. Mutant S202-pAcF Fab and Q389-pAcF IgG polymer conjugates specifically delivered siRNAs to HER2+ cells and mediated potent gene silencing at both the mRNA and protein levels. However, a mutant A121-pAcF IgG polymer conjugate, despite its high binding affinity to HER2 antigen, did not induce a significant RNA interference response in HER2+ cells, presumably due to steric interference with antigen binding and internalization. These results highlight the importance of conjugation site on the activity of antibody-polymer-based therapeutics and suggest that such chemically defined APCs may afford a useful targeted delivery platform for siRNAs or other nucleic acid-based therapies. [ABSTRACT FROM AUTHOR]

Supramolecular self-assembly and reversibleswitching has been demonstrated for the first time between monovalent and multivalent carbohydrate ligands and the multivalency effect on lectin binding has been investigated. The self-assembly process is mediated through noncovalent interactions between pendant moieties on a polymer scaffold and a monosaccharide-functionalized viologen with cucurbit[8]uril (CB[8]) acting as a “supramolecular handcuff”. The rate of binding of the tetrameric lectin Concanavalin A (Con A) to a mannose-containing supramolecular glycopolymer was investigated through a standard turbidimetric assay. [ABSTRACT FROM AUTHOR]

Oral delivery of previously disclosed purine and benzimidazole fructose-1,6-bisphosphatase (FBPase) inhibitors via prodrugs failed, which was likely due to their high molecular weight (>600). Therefore, a smaller scaffold was desired, and a series of phosphonic acid-containing thiazoles, which exhibited high potency against human liver FBPase (IC50of 10−30 nM) and high selectivity relative to other 5′-adenosinemonophosphate (AMP)-binding enzymes, were discovered using a structure-guided drug design approach. The initial lead compound (30j) produced profound glucose lowering in rodent models of type 2 diabetes mellitus (T2DM) after parenteral administration. Various phosphonate prodrugs were explored without success, until a novel phosphonic diamide prodrug approach was implemented, which delivered compound 30jwith good oral bioavailability (OBAV) (22−47%). Extensive lead optimization of both the thiazole FBPase inhibitors and their prodrugs culminated in the discovery of compound 35n(MB06322) as the first oral FBPase inhibitor advancing to human clinical trials as a potential treatment for T2DM. [ABSTRACT FROM AUTHOR]