High throughput ‘catch-and-release’ synthesis within spatially discrete gel arrays

A tetrafluorophenol acrylamide monomer unit was synthesised, co-polymerised and grafted onto a glass slide to form individual gel spots. As a proof of principle study, a small library of amides was rapidly synthesised within these gel spots using ‘catch-and-release’ chemistry, including the biologically interesting quorum sensing acyl-homoserine lactones. The tetrafluorophenol acrylamide gel provides an efficient platform to synthesise and screen small molecules for biological activity.     

Frontiers in catalytic nitrile hydration: Nitrile and cyanohydrin hydration catalyzed by homogeneous organometallic complexes

Acrylic monomers are a significant part of the global economy, contributing to the manufacture of over a billion tons of diverse polymeric consumer products every year. The development of more efficient, greener methods to manufacture this highly demanded class of compounds is an important goal in the realization of a sustainable chemical industry. The pursuit of environmentally benign production processes has inspired a rich body of industrial and academic research on methods for the catalytic hydration of nitriles, and this review surveys both established and newer methods of generating acrylic amides, acids, and esters from nitrile and cyanohydrin substrates. The review also examines synthetic and mechanistic studies of homogeneously catalyzed nitrile hydration reactions with an emphasis on explicating the parameters that impact catalyst performance. The final section is a discussion of catalyst properties, gleaned from the mechanistic studies, that will be useful in designing the next generation of nitrile hydration catalysts.     

Comparison of the Phenolic Compound Profile and Antioxidant Potential of Achillea atrata L. and Achillea millefolium L.

In the present study, Achillea atrata L. and A. millefolium L. were compared for the first time with regard to their phenolic compound profile and antioxidant activity by applying the 2,2-diphenyl-picryl hydrazyl radical assay. For this purpose, aerial plant parts were consecutively extracted with solvents of increasing polarity (dichloromethane, n-butanol, ethyl acetate), revealing that the A. atrata ethyl acetate fraction showed the highest antioxidant activity with an IC₅₀ value of 12.2 ± 0.29 µg/mL compared to 17.0 ± 0.26 µg/mL for A. millefolium. Both species revealed the presence of luteolin, apigenin, centaureidin, and nevadensin exclusively in this most polar fraction, which are known as effective 2,2-diphenyl-picryl hydrazyl radical scavengers. The antioxidant capacity of the aforementioned fractions strikingly correlated with their total phenolic contents, which was highest in the ethyl acetate fraction of A. atrata. Characterization of the metabolite profiles of both Achillea species showed only marginal differences in the presence of key compounds, whereas the concentrations of individual compounds appeared to be species-specific. Our results suggest that A. atrata, based on its compound pattern and bioactivity characteristics, has similar qualities for phytotherapy as A. millefolium.     

Partially Saturated Bicyclic Heteroaromatics as an sp3‐Enriched Fragment Collection

Fragment‐based lead generation has proven to be an effective means of identifying high‐quality lead compounds for drug discovery programs. However, the fragment screening sets often used are principally comprised of sp²‐rich aromatic compounds, which limits the structural (and hence biological) diversity of the library. Herein, we describe strategies for the synthesis of a series of partially saturated bicyclic heteroaromatic scaffolds with enhanced sp³ character. Subsequent derivatization led to a fragment collection featuring regio‐ and stereo‐controlled introduction of substituents on the saturated ring system, often with formation of new stereocenters.     

Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation

Peptide stapling is a robust strategy for generating enzymatically stable, macrocyclic peptides. The incorporation of biologically relevant tags (such as cell-penetrating motifs or fluorescent dyes) into peptides, while preserving their binding interactions and enhancing their stability, is highly sought after. Despite the unique opportunities offered by tryptophan‘s indole scaffold for targeted functionalisation, its utilisation in peptide stapling has been limited as compared to other amino acids. Herein, we present an approach for peptide stapling using the tryptophan-mediated Petasis reaction. This method enables the synthesis of both stapled and labelled peptides and is applicable to both solution and solid-phase synthesis. Importantly, the use of the Petasis reaction in combination with tryptophan facilitates the formation of stapled peptides in a straightforward, multicomponent fashion, while circumventing the formation of undesired by-products. Furthermore, this approach allows for efficient and diverse late-stage peptide modifications, thereby enabling rapid production of numerous conjugates for biological and medicinal applications.     

Gemmacin B: bringing diversity back into focus

Through the synthesis of a focused library and SAR investigations, a more potent analogue of gemmacin (discovered in a previous diversity-oriented synthesis (DOS) campaign), gemmacin B, was discovered.     

Diversity-oriented synthesis; a spectrum of approaches and results

Since our emerging area article, diversity-oriented synthesis (DOS), which aims to prepare efficiently collections of skeletally diverse small molecules, has developed in the synthetic approaches it employs. This article describes three general strategies, highlighting some successful examples. The utility of DOS, in the interrogation of chemical space and in the identification of novel biologically active lead compounds, is also discussed.     

Fluorescence measurements of duplex DNA oligomers under conditions conducive for forming M-DNA (a metal-DNA complex)

M-DNA (a metal complex of DNA with millimolar concentrations of Zn2+, Co2+, or Ni2+ and basic pH) has been proposed to undergo electron transfer over long distances along the helix and has generated interest as a potential building block for nanoelectronics. We show that DNA aggregates form under solvent conditions favorable for M-DNA (millimolar zinc and pH = 8.6) by fluorescence correlation spectroscopy. We have performed steady-state F?rster resonance energy transfer (FRET) experiments with DNA oligomers conjugated with 6-carboxyfluorescein and tetramethylrhodamine to the opposite ends of double-stranded DNA (dsDNA) molecules. Enhanced acceptor emission is observed for distances larger than expected for identical DNA molecules with no zinc. To avoid intermolecular FRET, the fluorescently labeled dsDNA is diluted with a 100-fold excess of unlabeled dsDNA. The intramolecular FRET efficiency increases 25-fold for a 30-mer doubly labeled duplex DNA molecule upon addition of millimolar concentrations of zinc ions. Without zinc, this oligomer has less than 1% FRET efficiency. This dramatic increase in the FRET efficiency points to either significant changes in the F?rster radius or fraying of the ends of the DNA helices. The latter hypothesis is supported by our experiments with a 9-mer that show dissociation of the duplex by zinc ions.     

Quantum: Einstein,Bohr and the Great Debate About the Nature of Reality,by Manjit Kumar

The history of absolute measurements of gravity is mentioned and the reasons for making absolute measurements are indicated. The principles and main advantages and difficulties of the main method—reversible pendulum, free fall, symmetrical free motion—are discussed and examples of each method are described. Problems of comparison of different determinations and of estimating systematic errors are considered.