Near-infrared absorption spectroscopy of toluene-sulfonate-diacetylene crystals

The near-infrared (NIR) absorption of toluene-sulfonate-diacetylene crystals (PTS) has been investigated during thermal polymerization. It is shown by comparative NIR and IR spectroscopy of deuterated and of protonated PTS at various temperatures, that these absorptions are vibronic in nature. They can be assigned unambiguously to distinct parts of the molecule. No low-lying electronic state has been found.     

Integramides A and B, two novel non-ribosomal linear peptides containing nine C(alpha)-methyl amino acids produced by fungal fermentations that are inhibitors of HIV-1 integrase

[structure: see text]. Integramides A and B are two novel 16-mer linear peptides rich in C(alpha)-methyl amino acids that were isolated from fungal extracts of Dendrodochium sp. by employing a bioassay-guided isolation procedure using recombinant HIV-1 integrase. The structure and stereochemistry were elucidated by a combination of 2D NMR and ESI- and FAB-MS including MS/MS studies and by Marfey's method. Integramides A and B inhibited the coupled reaction of HIV-1 integrase with IC50 values of 17 and 10 microM, respectively.     

Dynorphin A 1–17 biotransformation in inflamed tissue, serum and trypsin solution analysed by liquid chromatography–tandem mass spectrometry

Dynorphin A 1–17 (DYN A) is an endogenous neuropeptide that is of interest due to its diverse roles in analgesia, inflammation and addiction. Upon release, DYN A is subject to metabolism by a range of enzymes and its biotransformation is dependent on the site and environment into which it is released. In this study, we investigated the biotransformation of DYN A in rat inflamed tissue at pH?7.4 and 5.5, in rat serum and in trypsin solution. DYN A-porcine was incubated at 37?°C in each matrix over a range of incubation periods. The resultant fragments were separated using a C4 column and detected by mass spectrometry using total ion current mode. Incubation of DYN A in trypsin solution and in rat serum resulted in 6 and 14 fragments, respectively. Incubation in inflamed rat paw tissue occasioned 21 fragments at pH?7.4 and 31 fragments at pH?5.5. Secondary breakdown of some larger primary fragments was also observed in this study.     

Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3

The chemokines (CXCL9, CXCL10 and CXCL11) and associated CXCR3 receptor are expressed during the inflammatory process from multiple sclerosis, atherosclerosis or organ transplantation resulting in the recruitment of lymphocytes leading to tissue damage. It is hypothesized that blocking of the ligand/CXCR3 receptor interaction has potential to provide opportunity for development of agents that would block tissue rejection. In this paper, four classes of natural product inhibitors (IC₅₀ ranging 0.1–41 M) have been described that block the CXCR3 receptor interaction of IP-10 ligand. These include a cyclic thiopeptide (duramycin), polyketide glycosides (roselipins), steroidal glycosides (hypoglausin A and dioscin) and a novel alkyl pyridinium alkaloid that were isolated by bioassay-guided fractionation of the organic extracts derived from actinomycete, fungal, plant and marine sources and discovered using ¹²⁵ I IP-10/CXCR3 binding assay. Duramycin was the most potent with an IC₅₀ of 0.1 M. Roselipins 2A, 2B and 1A showed IC₅₀ values of 14.6, 23.5, and 41 M, respectively. Diosgenin glycosides dioscin, hypoglaucin A and kallstroemin D exhibited IC₅₀ values of 2.1, 0.47 and 3 M, respectively. A novel cyclic 3-alkyl pyridinium salt isolated from a sponge displayed a binding IC₅₀ of 0.67 M.     

Thio acid-mediated conversion of azides to amides – Exploratory studies en route to oroidin alkaloids

The utility of the thio acid-azide coupling reaction to afford amides is explored in imidazole-containing substrates for application in the total synthesis of examples of oroidin alkaloids. Good yields of the expected amides are obtained in both monomeric and dimeric substrates. Bis azides react preferentially at the 2-azido position but hydrosulfenylation and reduction interfere. 2-Thiophenyl and 2-oxo groups were evaluated as 2-amino surrogates, the thioether delivered the expected amide, whereas 2-imidazolone gave a mixture of the expected amide and the hydrosulfenylation product.     

Potential of Biocellulose Nanofibers Production from Agricultural Renewable Resources: Preliminary Study

In the present preliminary study, we report results for the biocellulose nanofibres production by Gluconacetobacter xylinus. Production was examined by utilizing different feedstocks of single sugars and sugar mixtures with compositions similar to the acid hydrolyzates of different agriculture residues. Profiles for cell proliferation, sugar consumption, and the subsequent pH changes were thoroughly analyzed. Highest biocellulose production of 5.65 g/L was achieved in fructose medium with total sugar consumption of 95.57%. Moreover, the highest production using sugar mixtures was 5.2 g/L, which was achieved in feedstock with composition identical to the acid hydrolyzate of wheat straws. This represented the highest biocellulose yield of 17.72 g/g sugars compared with 14.77 g/g fructose. The lowest production of 1.1 and 1.75 g/L were obtained in xylose and glucose media, respectively, while sucrose and arabinose media achieved relatively higher production of 4.7 and 4.1 g/L, respectively. Deviation in pH of the fermentation broths from the optimum value of 4–5 generally had marked effect on biocellulose production with single sugars in feedstock. However, the final pH values recorded in the different sugar mixtures were ～3.3–3.4, which had lower effect on production hindrance. Analyzing profiles for sugars' concentrations and cell growth showed that large amount of the metabolized sugars were mainly utilized for bacterial cell growth and maintenance, rather than biocellulose production. This was clearly observed with single sugars of low production, while sugar consumption was rather utilized for biocellulose production with sugar mixtures. Results reported in this study demonstrate that agriculture residues might be used as potential feedstocks for the biocellulose nanofibres production. Not only this represents a renewable source of feedstock, but also might lead to major improvements in production if proper supplements and control were utilized in the fermentation process.     

Effect of solvent and electrospray mass spectrometer parameters on the charge state distribution of peptides--a case study using liquid chromatography/mass spectrometry method development for beta-endorphin assay

Beta-endorphin was used as a model peptide to study the effect of solvent and electrospray mass spectrometer parameters in the optimisation of an assay method for multiply charged compounds using liquid chromatography/mass spectrometry (LC/MS). Unlike with singly charged compounds, the charge state distribution has a significant impact in the method development of multiply charged compounds such as peptides. Using a 50% acetonitrile/water solvent mixture, we found that the ion spray voltage had no influence on the charge state distribution. However, increasing declustering potential led to deprotonation of the higher charge states of the peptide thus causing a shift to lower charge states. The mechanism leading to the deprotonation was examined. It was concluded that the deprotonation is due to endoergic proton transfer from the peptide to solvent molecules clustered to the peptide that occurs in the declustering region. The extent of deprotonation increases with increasing proton affinity of the molecules of the non-aqueous solvent component used. Thus, if desired, deprotonation can be avoided by selecting a low proton affinity solvent such as methanol. The focusing potential was also found to have a great influence on the charge state distribution observed. The results of this study enabled us to select the optimum ion to be used in single ion/reaction monitoring mode. They also provided the most favourable parameter values to be used in the method to obtain the best sensitivity for the ion of choice. The results demonstrate the importance of considering the charge state distribution in the optimisation of electrospray LC/MS methods for multiply charged compounds.     

Effect of ionization suppression by trace impurities in mobile phase water on the accuracy of quantification by high‐performance liquid chromatography/mass spectrometry

The high‐performance liquid chromatography (HPLC) column is capable of enrichment/pre‐concentration of trace impurities in the mobile phase during the column equilibration, prior to sample injection and elution. These impurities elute during gradient elution and result in significant chromatographic peaks. Three types of purified water were tested for their impurity levels, and hence their performances as mobile phase, in HPLC followed by total ion current (TIC) mode of MS. Two types of HPLC‐grade water produced 3–4 significant peaks in solvent blanks while LC/MS‐grade water produced no peaks (although peaks were produced by LC/MS‐grade water also after a few days of standing). None of the three waters produced peaks in HPLC followed by UV‐Vis detection. These peaks, if co‐eluted with analyte, are capable of suppressing or enhancing the analyte signal in a MS detector. As it is not common practice to run solvent blanks in TIC mode, when quantification is commonly carried out using single ion monitoring (SIM) or single or multiple reaction monitoring (SRM or MRM), the effect of co‐eluting impurities on the analyte signal and hence on the accuracy of the results is often unknown to the analyst. Running solvent blanks in TIC mode, regardless of the MS mode used for quantification, is essential in order to detect this problem and to take subsequent precautions. Copyright © 2010 John Wiley & Sons, Ltd.