Radiation synthesis of superabsorbent poly(acrylic acid)–carrageenan hydrogels

A series of superabsorbent hydrogels were prepared from carrageenan and partially neutralized acrylic acid by gamma irradiation at room temperature. The gel fraction, swelling kinetics and the equilibrium degree of swelling (EDS) of the hydrogels were studied. It was found that the incorporation of even 1% carrageenan (sodium salt) increases the EDS of the hydrogels from 320 to 800 g/g. Thermal analysis were carried out to determine the amount of free water and bound water in the hydrogels. Under optimum conditions, poly(acrylic acid)–carrageenan hydrogels with high gel fraction (80%) and very high EDS (800 g/g) were prepared gamma radiolytically from aqueous solution containing 15% partially neutralized acrylic acid and 1–5% carrageenan. The hydrogels were also found to be sensitive to the pH and the ionic strength of the medium.     

Nucleophilic displacement at benzhydryl centers: asymmetric synthesis of 1,1-diarylalkyl derivatives

[reaction: see text] Activation of substituted 1,1-diarylmethanols as their corresponding toluenesulfonates and subsequent displacement with a range of carbon, nitrogen, oxygen, and sulfur nucleophiles proceeds in 81-96% yield. Enantiomerically enriched diarylmethanols 8a-c were activated and displaced with pyridine acetate enolate with complete stereochemical inversion at carbon to yield 1,1-diarylalkyl derivatives 10a-c without loss of optical purity.     

Probing the glycosidic linkage: UV and IR ion-dip spectroscopy of a lactoside

The beta(1-->4) glycosidic linkage found in lactose is a prevalent structural motif in many carbohydrates and glycoconjugates. Using UV and IR ion-dip spectroscopies to probe benzyl lactoside isolated in the gas phase, we find that the disaccharide unit adopts only a single, rigid structure. Its fully resolved infrared ion-dip spectrum is in excellent agreement with that of the global minimum structure computed ab initio. This has glycosidic torsion angles of phi(H) (H1-C1-O-C4') approximately 180 degrees and psi(H) (C1-O-C4'-H4') approximately 0 degrees which correspond to a rotation of approximately 150 degrees about the glycosidic bond compared to the accepted solution-phase conformation. We discuss the biological implications of this discovery and the generality of the strategies employed in making it.     

Detecting proximities between quadrupolar nuclei by double-quantum NMR

A robust, easy to optimize, and efficient homonuclear correlation NMR experiment for half-integer quadrupolar nuclei in solids is described and has been experimentally tested on anhydrous Na2HPO4-(23Na, S= 3/2 nucleus) and as-synthesized AlPO4-14 (27Al, S= 5/2 nucleus), an aluminophosphate molecular sieve.     

Characterization of low-molecular weight peptides in champagne wine by liquid chromatography/tandem mass spectrometry

This paper reports the use of an on-line LC–ESI–MS/MS method for the identification and quantification of di- and tripeptides in champagne wine without laborious sample pretreatment. The identification of these compounds, in their underivatised form, is based on identical retention times and ESI–MS spectra to those of reference standards. The presence of nine dipeptides (Arg–Ile, Ile–Arg, Ile–Val, Lys–Phe, Lys–Tyr, Phe–Lys, Tyr–Gln, Tyr–Lys, Val–Ile) and the absence of two tripeptides (Phe–Arg–Arg and Lys–Met–Asn) have been evidenced in the matrix. Calibration curves for each analyte were established using Phe–Arg as internal standard. The calibration curves were linear in the concentration range 0.1–10 mg L⁻¹ with a determination coefficient, r², better than 0.992. The accuracy for the calibration standard was estimated at between 92 and 102%. This method allows high recovery and satisfies the necessary requirements with respect to accuracy, repeatability and sensitivity. The first application of this analytical method to the measurement of di- and tri-peptides in different vintages of champagne wine is reported. Compositional changes in the peptides occurred depending on the vintage.     

Switching from linear to cyclic δ‐Polyvalerolactone synthesized via zeolitic imidazolate framework as a catalyst: A promising approach

A series of spray dried zeolitic imidazolate frameworks (ZIFs = ZIF‐8, ZIF‐67, and Zn/Co‐ZIF) are used as a catalyst for the bulk ring‐opening polymerization of δ‐valerolactone without any co‐catalyst to generate polyvalerolactone. Interestingly, using the same catalyst under the same reaction conditions could manipulate the structure of the product polymer, and thus its physical properties. Thus, using a dried substrate leads to the formation of the cyclic polymer while a linear polymer was formed on using the commercially available substrate. An activated monomer mechanism has been suggested where the propagating zinc alkoxide undergoes an intramolecular transesterification to release cyclic or linear polyvalerolactone. The ROP of δ‐VL without drying shows that the polymeric zwitterions have little tendency to cyclize in the presence of moisture. At 140 °C, ZIF‐8 shows a superior catalytic activity resulting in the production of cyclic polyvalerolactone having a high molecular weight as compared to ZIF‐67 or Zn/Co‐ZIF due to the presence of highly active sites. The catalyst could be recycled and reused without any significant loss of catalytic activity.     

The promise of electrochemical impedance spectroscopy as novel technology for the management of patients with diabetes mellitus

Self-monitoring of blood glucose is the standard of care in management of hyperglycemia among patients with diabetes mellitus. To increase the sensitivity and specificity of current devices, a novel method of detecting glucose using electrochemical impedance spectroscopy (EIS) technology is explored. The enzyme glucose oxidase (GOx) was fixed to gold electrodes and a sine wave of sweeping frequencies was induced using a wide range of concentrations of glucose. Each frequency in the impedance sweep was analyzed for the highest response and R-squared value. The frequency with both factors optimized is specific for the glucose-GOx binding interaction and was determined to be 1.17 kHz in purified solutions in both higher and lower ranges of glucose. The correlation between the impedance response and concentration at the low range of detection (0-100 mg dL(-1) of glucose) was determined to be 3.53 ohm/ln (mg dL(-1)) with an R-squared value of 0.90 with a 39 mg dL(-1) lower limit of detection. The same frequency of 1.17 kHz was verified in whole blood under the same glucose range. The above data confirm that EIS offers a new method of glucose detection as an alternative to current technology in use by patients. Additionally, the unique frequency response of individual markers allows for modulation of signals so that several other markers important in the management of diabetes could be measured with a single sensor.     

O(4)-Alkyl-2'-deoxythymidine cross-linked DNA to probe recognition and repair by O(6)-alkylguanine DNA alkyltransferases

DNA duplexes containing a directly opposed O(4)-2'-deoxythymidine-alkyl-O(4)-2'-deoxythymidine (O(4)-dT-alkyl-O(4)-dT) interstrand cross-link (ICL) have been prepared by the synthesis of cross-linked nucleoside dimers which were converted to phosphoramidites to produce site specific ICL. ICL duplexes containing alkyl chains of four and seven methylene groups were prepared and characterized by mass spectrometry and nuclease digests. Thermal denaturation experiments revealed four and seven methylene containing ICL increased the T(m) of the duplex with respect to the non-cross-linked control with an observed decrease in enthalpy based on thermodynamic analysis of the denaturation curves. Circular dichroism experiments on the ICL duplexes indicated minimal difference from B-form DNA structure. These ICL were used for DNA repair studies with O(6)-alkylguanine DNA alkyltransferase (AGT) proteins from human (hAGT) and E. coli (Ada-C and OGT), whose purpose is to remove O(6)-alkylguanine and in some cases O(4)-alkylthymine lesions. It has been previously shown that hAGT can repair O(6)-2'-deoxyguanosine-alkyl-O(6)-2'-deoxyguanosine ICL. The O(4)-dT-alkyl-O(4)-dT ICL prepared in this study were found to evade repair by hAGT, OGT and Ada-C. Electromobility shift assay (EMSA) results indicated that the absence of any repair by hAGT was not a result of binding. OGT was the only AGT to show activity in the repair of oligonucleotides containing the mono-adducts O(4)-butyl-4-ol-2'-deoxythymidine and O(4)-heptyl-7-ol-2'-deoxythymidine. Binding experiments conducted with hAGT demonstrated that the protein bound O(4)-alkylthymine lesions with similar affinities to O(6)-methylguanine, which hAGT repairs efficiently, suggesting the lack of O(4)-alkylthymine repair by hAGT is not a function of recognition.     

CRDOCK: An Ultrafast Multipurpose Protein-Ligand Docking Tool

An ultrafast docking and virtual screening program, CRDOCK, is presented that contains (1) a search engine that can use a variety of sampling methods and an initial energy evaluation function, (2) several energy minimization algorithms for fine tuning the binding poses, and (3) different scoring functions. This modularity ensures the easy configuration of custom-made protocols that can be optimized depending on the problem in hand. CRDOCK employs a precomputed library of ligand conformations that are initially generated from one-dimensional SMILES strings. Testing CRDOCK on two widely used benchmarks, the ASTEX diverse set and the Directory of Useful Decoys, yielded a success rate of ～75% in pose prediction and an average AUC of 0.66. A typical ligand can be docked, on average, in just ～13 s. Extension to a representative group of pharmacologically relevant G protein-coupled receptors that have been recently cocrystallized with some selective ligands allowed us to demonstrate the utility of this tool and also highlight some current limitations. CRDOCK is now included within VSDMIP, our integrated platform for drug discovery.     

Phosphatase-triggered fusogenic liposomes for cytoplasmic delivery of cell-impermeable compounds

License to fuse! A phosphorylated fusion peptide can mediate membrane fusion when the phosphates (green triangles, see scheme) are removed by phosphatases (blue spheres), delivering the contents of the liposome into the cytosol. This phosphatase-triggered approach may be useful to create target-specific lipid nanocarriers.