New 4-pentafluorosulfanyl and 4-perfluoroalkylthio derivatives of 1-chloro-2-nitro- and 1-chloro-2,6-dinitrobenzenes

New 4-pentafluorosulfanyl and 4-perfluoroalkylthio derivatives of 1-chloro-2-nitrobenzene and 1-chloro-2,6-dinitrobenzene were prepared from the corresponding bis(4-chloro-3-nitrophenyl)disulfide and bis(4-chloro-3,5-dinitrophenyl)disulfide, respectively. The SF₅ derivatives were obtained by fluorination of the disulfides with AgF₂ according to Sheppard’s method, while perfluoroalkylation was carried out by means of thermolytic reactions with xenon(II) bis(perfluoroalkylcarboxylates). The introduction of fluorine-containing, electron-withdrawing substituents into the aromatic ring (in the presence of other deactivating groups) reinforces the activation of the halogen substituent towards nucleophilic attack. Several nucleophilic substitution reactions have been carried out with these compounds, and as a result, some N- and S-containing groups were introduced in the benzene ring. For example, the previously unknown SF₅, CF₃S, and C₂F₅S analogues of trifluralin (Treflan^®) were prepared and characterized. Additional synthetic possibilities for heterocyclic chemistry are presented on the basis of reactions of the new 1-chloro-2,6-dinitrobenzene derivatives with ethyl thioglycolate wherein fluorine-containing derivatives of benzothiazole N-oxide were obtained as the main products.     

The heterogeneity of the glycosylation of alpha-1-acid glycoprotein between the sera and synovial fluid in rheumatoid arthritis

Alpha-1-acid glycoprotein (AGP) is a plasma glycoprotein produced by the liver that undergoes increased production and altered glycosylation in several physiological and pathological conditions including rheumatoid arthritis. To date, although present in the synovial fluid of rheumatoid arthritis patients, there has been no evidence for the separate extra-hepatic production of AGP. This study indicates that there could be a localized production of AGP in rheumatoid synovial fluid by demonstrating that the glycosylation patterns of AGP differed between the serum and synovial fluid in the same rheumatoid patient. Serum AGP was largely composed of fucosylated tri- and tetra-antennary oligosaccharide chains while the synovial fluid contained mainly bi-antennary chains that were fucosylated to a lesser extent. This structural heterogeneity of glycosylation resulted in functional diversity; serum but not synovial AGP is able to inhibit binding to the cell adhesion molecule E-selectin through expression of antigen sialyl Lewis X.     

DNA-based photonic logic gates: AND,NAND, and INHIBIT

Conventional microprocessors use elementary logic gates to perform complex computational tasks. Mimicking such computational processes using purely molecular systems has been limited in most cases by the lack of design generality or potential addressability of existing molecular logic gates. Herein we report that by employing the universal recognition properties of DNA simple photonic logic gates can be created that are capable of AND, NAND, and INHIBIT logic operations.     

Building functionalized peptidomimetics: new electroauxiliaries and the use of a chemical oxidant for introducing N-acyliminium ions into peptides

[reaction: see text] The removal of electroauxiliaries from peptide substrates with chemical oxidants has been examined as a method for inserting N-acyliminium ions into the peptides. To this end, it was found that both 4-methoxyphenyldimethylsilyl and 2,4-dimethoxyphenyldimethylsilyl electroauxiliaries were readily cleaved with the use of ceric ammonium nitrate. Of the two groups, the 2,4-dimethoxyphenyldimethylsilyl electroauxiliary was the most labile under the oxidative conditions. The oxidation reactions were shown to be compatible with the use of a solid-phase substrate.     

A photopatternable pentacene precursor for use in organic thin-film transistors

We demonstrate that modifying pentacene to incorporate an acid-labile moiety into its molecular structure leads to a new precursor that can be easily deposited, photopatterned, and processed via wet-chemical methods to produce organic semiconducting devices exhibiting good electrical characteristics. Acidic conditions produced by ultraviolet illumination of a co-deposited photoacid generator greatly accelerate the local conversion of this N-sulfinyl-tert-butylcarbamate pentacene adduct back to pentacene. Photopatterned thin-film transistors exhibit carrier mobilities in excess of 0.1 cm2 V-1 s-1, making this an attractive precursor for fabrication of large-area organic electronics via solution-phase methods.     

An asymmetric synthesis of both enantiomers of the indole alkaloid deplancheine

We report a novel, facile and asymmetric approach to both enantiomers of the indole alkaloid deplancheine from a readily available, nonracemic chiral template. The natural product and its antipode are isolated with >95% ee.     

Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria

The increasing occurrence of multi-antibiotic resistant microbes has led to the search for alternative methods of killing pathogens and treating infections. Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill mammalian and microbial cells. Although the photodynamic inactivation of bacteria has been known for over a hundred years, its use to treat infections has not been much developed. This may be partly due to the difficulty of monitoring the effectiveness of PDT in animal models of infection. In order to facilitate this monitoring process, we have developed a procedure that uses bioluminescent genetically engineered bacteria and a light sensitive imaging system to allow real-time visualization of infections. When these bacteria are treated with PDT in vitro, the loss of luminescence parallels the loss of colony-forming ability. We have developed several models of infections in wounds and soft-tissue abscesses in mice that can be followed by bioluminescence imaging. The size and intensity of the infection can be sequentially monitored in a non-invasive fashion in individual mice in real-time. When photosensitizers are introduced into the infected tissue followed by illumination with red light, a light-dose dependent loss of luminescence is seen. If the bacterium is invasive, the loss of luminescence correlates with increased survival of the mice, whilst animals in control groups die of sepsis within five days. Healing of the PDT treated wounds is not impaired and may actually be improved. This approach can allow many animal models of localized infections to be accurately monitored for efficacy of treatment by PDT.     

Alkyl Ether Analogs of Chlorophyll-a Derivatives: Part 1. Synthesis, Photophysical Properties and Photodynamic Efficacy

The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-a analogs are described. For short-chain carbon ethers (1–7carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n-hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1-bromoethyl)-2-devinylpyropheophorbide-a with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-a analogs were found to be more active than related chlorin e₆ derivatives, in which the isocyclic ring (ring “E”) was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-a analogs. The photosensitizers prepared from pyropheophorbide-a methyl ester and chlorin e₆ trimethyl ester have long wavelength absorption at 660 nm (ε 45000 to 50000). Reduction of the carbonyl group in the pyropheophorbide-a to methylene (ring E) resulted in a blue shift to 648 nm (ε 38000).