Phosphate diester hydrolysis is strongly accelerated, by a factor of 104, in the presence of artificial enzymes especially designed in the light of spatiotemporal concepts, anchoring imidazoles in a pillar[5]­arene matrix. Host:guest complexes cleave the aryl phosphodiesters via nucleophilic attack of the properly placed imidazole moieties with the release of 2,4-dinitrophenolate and the formation of unstable phosphoroamidates that regenerate the catalyst and 2,4-dinitrophenyl phosphate. Comparison of the reactivity of P5IMD with that of imidazole shows a 270-fold increase. Asymmetrical diesters allow the formation of two different docking structures of the host:guest complex, with just one being reactive and allowing selectivity increases of 102-fold, compared with the reaction in bulk water of the same asymmetrical diesters.

The reaction mechanism of the GPx-like oxidation of PhSH with H(2)O(2) catalyzed by selenoxides proceeds via formation of the hydroxy perhydroxy selenane, which is a stronger oxidizing agent than selenoxide. A hydroxy perhydroxy selenane intermediate was observed by electrospray ionization mass spectrometry and (77)Se NMR spectroscopy in reactions of selenoxide 8 with H(2)O(2).The initial velocity of oxidation of PhSH by H(2)O(2) with selenoxide 8 is 4 orders of magnitude higher than that of 8 without peroxide. Selenoxide 8 is not reduced to selenide 6 by PhSH in the presence of H(2)O(2). While electronic substituent effects have minimal impact on the catalytic performance of selenoxides, chelating groups increase the rate of catalysis.

Key aspects for the development of a greener synthesis and the use of the organoselenium compounds.

Biocatalysts represent an efficient, highly selective and greener alternative to metal catalysts in both industry and academia. In the last two decades, the interest in biocatalytic transformations has increased due to an urgent need for more sustainable industrial processes that comply with the principles of green chemistry. Thanks to the recent advances in biotechnologies, protein engineering and the Nobel prize awarded concept of direct enzymatic evolution, the synthetic enzymatic toolbox has expanded significantly. In particular, the implementation of biocatalysts in continuous flow systems has attracted much attention, especially from industry. The advantages of flow chemistry enable biosynthesis to overcome well-known limitations of “classic” enzymatic catalysis, such as time-consuming work-ups and enzyme inhibition, as well as difficult scale-up and process intensifications. Moreover, continuous flow biocatalysis provides access to practical, economical and more sustainable synthetic pathways, an important aspect for the future of pharmaceutical companies if they want to compete in the market while complying with European Medicines Agency (EMA), Food and Drug Administration (FDA) and green chemistry requirements. This review focuses on the most recent advances in the use of flow biocatalysis for the synthesis of active pharmaceutical ingredients (APIs), pharmaceuticals and natural products, and the advantages and limitations are discussed.

BackgroundOrganoselenium compounds have antimicrobial activity against some bacteria and fungi; furthermore, the antioxidant activity of diselenides has been demonstrated. The aim of the present work was to examine the in vitro minimal inhibitory concentration of a panel of differently substituted diselenides and their effectiveness in inhibiting biofilm formation and dispersing preformed microbial biofilm of Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa and the yeast Candida albicans, all involved in wound infections. Moreover, the cytotoxicity of the compounds was determined in human dermal fibroblast and keratinocytes. In closing, we tested their direct antioxidant activity.ResultsDiselenides showed different antimicrobial activity, depending on the microorganism. All diselenides demonstrated a good antibiofilm activity against S. aureus and S. epidermidis, the compounds camphor diselenide, bis[ethyl-N-(2’-selenobenzoyl) glycinate] and bis[2’-seleno-N-(1-methyl-2-phenylethyl) benzamide] were active against S. pyogenes and C. albicans biofilm while only diselenides 2,2’-diselenidyldibenzoic acid and bis[ethyl-N-(2’-selenobenzoyl) glycinate] were effective against P. aeruginosa. Moreover, the compounds bis[ethyl-N-(2’-selenobenzoyl) glycinate] and bis[2’-seleno-N-(1-methyl-2-phenylethyl) benzamide] showed an antioxidant activity at concentrations lower than the 50 % of cytotoxic concentration.ConclusionsBecause microbial biofilms are implicated in chronic infection of wounds and treatment failure, the combination of antimicrobial activity and potential radical scavenging effects may contribute to the improvement of wound healing. Therefore, this study suggests that bis[ethylN-(2’-selenobenzoyl) glycinate] and bis[2’-seleno-N-(1-methyl-2-phenylethyl) benzamide] are promising compounds to be used in preventing and treating microbial wound infections.