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Glycosylated diazeniumdiolates of structure R 2NN(O)NO-R' (R' = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R 2NN(O)NO (-) ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R 2NN(O)NO-GlcNAc (where R 2N = diethylamino or pyrrolidin-l-yl and GlcNAc = N-acetylglucosamin-l-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity.

Diazeniumdiolate anions and their prodrug forms are reliable sources of nitric oxide (NO) that have generated interest as promising therapeutic agents. A number of structural analogues of O(2)-(2,4-dinitro-5-(4-(N-methylamino)benzoyloxy)phenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate (PABA/NO), an anti-cancer lead compound that is designed to release NO upon activation by glutathione, were prepared. The nitric oxide release patterns of these O(2)-(2,4-dinitrophenyl) diazeniumdiolates in the presence of glutathione were tested and it was found that in the absence of competing pathways, these compounds release nearly quantitative amounts of NO. The ability of PABA/NO and its structural analogues to inhibit human leukemia cell proliferation was determined and it was found that compounds releasing elevated amounts of NO displayed superior cytotoxic effects.

They seem to be in a never-ending free fall: every month, in an almost dramatic way, the traditional print media in Germany and nearly every western industrial nation are losing circulation and, most of all, influence on their readers. Over decades, the consumers in the country of the world travel champions have learned, lived and loved the traditional media – this attitude is changing. With an unprecedented consistency, consumers are turning away from the print media, leaving front row seats to Facebook, YouTube and other social networks. New forms of communication are infiltrating areas to which nobody had access before and are becoming a part of our everyday life, replacing daily newspapers and magazines. The challenge for the travel industry is that only news and messages with an explicit access authorisation are admitted to this intimate zone. The reshuffled cards in the world of information confront an industry which has not yet shown a particular willingness to innovate with one of the most urgent questions ever: how can we reach the customers of today – and especially the customers of tomorrow – when the old media cannot address them anymore and readers trust recommendations on the internet more than their newspaper? In 2010, it will not take a lot of foresight or even courage to predict reliably who will win the race, online or print media. When it comes to the purchase decision for a vacation, the prize of information superiority goes extensively to the electronic media on the internet already today. However, we still do not know how long this process of change will take. How much longer can the industry rely on the “young seniors” and their familiar consumer behaviour? What course needs to be set today to win the consumer’s favour in order to be successful tomorrow? Where in the web do dangers lurk? In times when journalism becomes “partially weaker”, as the German journalist Peter Vos stated, public relations is facing numerous new tasks. It is true that PR experts will have to reposition themselves to persist in the altered marketing mix. One thing is beyond question: the new democratic form of communication in every direction is a one-way street – there is definitely no going back to the old rules of the game!

Although there are considerable data demonstrating that quantum mechanical hydrogen tunneling (HT) occurs in both enzymatic and nonenzymatic systems, little data exist that address the question of whether enzymes enhance the amount of HT relative to the corresponding nonenzymatic reactions. To investigate whether 3-oxo-Delta (5)-steroid isomerase (ketosteroid isomerase, KSI) enhances HT relative to the nonenzymatic (acetate-catalyzed) isomerization of Delta (5)-androstene-3,17-dione ( 1) to Delta (4)-androstene-3,17-dione ( 3), alpha-secondary deuterium kinetic isotope effects (KIE) at C-6 of the steroid were determined for both the KSI- and acetate-catalyzed isomerizations. The normal intrinsic secondary KIE for both wild type (WT) KSI (1.073 +/- 0.023) and acetate (1.031 +/- 0.010) suggest the possibility of coupled motion (CM)/HT in both the enzymatic and nonenzymatic systems. To assess the contribution of CM/HT in these reactions, the secondary KIE were also measured under conditions in which deuterium instead of hydrogen is transferred. The decrease in secondary KIE for WT (1.035 +/- 0.011) indicates the presence of CM/HT in the enzymatic reaction, whereas the acetate reaction shows no change in secondary KIE for deuterium transfer (1.030 +/- 0.009) and therefore no evidence for CM/HT. On the basis of these experiments, we propose that KSI enhances the CM/HT contribution to the rate acceleration over the solution reaction. Active site mutants of KSI (Y14F and D99A) yield secondary KIEs similar to that of WT, indicating that mutations at the hydrogen-bonding residues do not significantly decrease the contribution of CM/HT to the KSI reaction.