Synthesis and Biological Evaluation of Several Dephosphonated Analogues of CMP‐Neu5Ac as Inhibitors of GM3‐Synthase

Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP‐Neu5Ac congeners and their anti ‐ GM3‐synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3‐synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade.     

Recent developments in computer vision-based analytical chemistry: A tutorial review

Chemical analysis based on colour changes recorded with imaging devices is gaining increasing interest. This is due to its several significant advantages, such as simplicity of use, and the fact that it is easily combinable with portable and widely distributed imaging devices, resulting in friendly analytical procedures in many areas that demand out-of-lab applications for in situ and real-time monitoring. This tutorial review covers computer vision-based analytical (CVAC) procedures and systems from 2005 to 2015, a period of time when 87.5% of the papers on this topic were published. The background regarding colour spaces and recent analytical system architectures of interest in analytical chemistry is presented in the form of a tutorial. Moreover, issues regarding images, such as the influence of illuminants, and the most relevant techniques for processing and analysing digital images are addressed. Some of the most relevant applications are then detailed, highlighting their main characteristics. Finally, our opinion about future perspectives is discussed.     

1,3‐Benzothiazoles as Antimicrobial Agents

Starting from 2‐amino‐1,3‐mercaptobenzothiazoles recently reported ( 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h ), a series of the corresponding 2‐mercapto‐1,3‐benzothiazole isosters ( 2a , 2b , 2c , 2d , 2e , 2f , 2g , 2h ) were screened for their in vitro antibacterial and antifungal activities. Results underline that the presence of the mercapto moiety at the 2‐position of the heterocyclic nucleus is crucial for activity against bacteria. The biological screening against Candida spp. identified commercial 2f as the most promising compound as antifungal against Candida albicans and tropicalis. Molecular modeling studies supported these results. Then, to enlarge structure‐activity relationship (SAR) studies on series 1 , newly synthesized compounds ( 1k , 1l , 1m , 1n , 1o , 1p ) were reported. All the compounds belonging to this series and bearing a bulky substituent at the 6‐position of the aryl moiety showed high antifungal activity.     

Dividing a complex reaction involving a hypervalent iodine reagent into three limiting mechanisms by ab initio molecular dynamics

The electrophilic N‐trifluoromethylation of MeCN with a hypervalent iodine reagent to form a nitrilium ion, that is rapidly trapped by an azole nucleophile, is thought to occur via reductive elimination (RE). A recent study showed that, depending on the solvent representation, the S_N2 is favoured to a different extent over the RE. However, there is a discriminative solvent effect present, which calls for a statistical mechanics approach to fully account for the entropic contributions. In this study, we perform metadynamic simulations for two trifluoromethylation reactions (with N‐ and S‐nucleophiles), showing that the RE mechanism is always favoured in MeCN solution. These computations also indicate that a radical mechanism (single electron transfer) may play an important role. The computational protocol based on accelerated molecular dynamics for the exploration of the free energy surface is transferable and will be applied to similar reactions to investigate other electrophiles on the reagent. Based on the activation parameters determined, this approach also gives insight into the mechanistic details of the trifluoromethylation and shows that these commonly known mechanisms mark the limits within which the reaction proceeds. © 2015 Wiley Periodicals, Inc.     

Kinetic Buffers

This paper proposes a new type of molecular device that is able to act as an inverse proton sponge to slowly decrease the pH inside a reaction vessel. This makes the automatic monitoring of the concentration of pH‐sensitive systems possible. The device is a composite formed of an alkyl chloride, which kinetically produces acidity, and a buffer that thermodynamically modulates the variation in pH value. Profiles of pH versus time (pH–t plots) have been generated under various experimental conditions by computer simulation, and the device has been tested by carrying out automatic spectrophotometric titrations, without using an autoburette. To underline the wide variety of possible applications, this new system has been used to realize and monitor HCl uptake by a di‐copper(II) bistren complex in a single run, in a completely automatic experiment.     

Ultrasound‐assisted extraction method for the simultaneous determination of emerging contaminants in freshwater sediments

Sediments are the fate of several emerging organic contaminants, such as pharmaceuticals, personal care products and hormones, and therefore an important subject in environmental monitoring studies. In the present work, a simple and sensitive method was developed, validated and applied for the simultaneous extraction of atenolol, caffeine, carbamazepine, diclofenac, ibuprofen, naproxen, propranolol, triclosan, estrone, 17‐β‐estradiol and 17‐α‐ethinylestradiol using ultrasound‐assisted extraction from freshwater sediment samples followed by solid‐phase extraction clean‐up and liquid chromatography with tandem mass spectrometry detection. The solvent type and extraction pH were evaluated to obtain the highest recoveries of the compounds. The best method shows absolute recoveries between 54.0 and 94.4% at 50 ng/g concentration. The method exhibits good precision with relative standard deviation ranging from 1.0–16%. The detection and quantification limits ranged from 0.006–0.067 and 0.016–0.336 ng/g, respectively. The developed method was successfully applied to freshwater sediment samples collected from different sites in Jundiaí River basin of São Paulo State, Brazil. The compounds atenolol, caffeine, propranolol and triclosan were detected in all the sampling sites with concentrations of 13.8, 41.0, 28.5 and 176 ng/g, respectively.