The selective incorporation of fluorinated motifs, in particular CF₂FG (FG=a functional group) and CF₂H groups, into organic compounds has attrracted increasing attention since organofluorine molecules are of the utmost importance in the areas of nuclear imaging, pharmaceutical, agrochemical, and material sciences. A variety of synthetic approaches has been employed in late‐stage difluoroalkylation reactions. Visible light photoredox catalysis for the production of CF₂FG and CF₂H radicals has provided a more sustainable alternative to other conventional radical‐triggered reactions from the viewpoint of safety, cost, availability, and “green” chemistry. A wide range of difluoroalkylating reagents has been successfully implemented in these organic transformations in the presence of transition metal complexes or organic photocatalysts. In most cases, upon excitation via visible light irradiation with fluorescent light bulbs or blue light‐emitting diode (LED) lamps, these photocatalysts can act as both reductive and oxidative quenchers, thus enabling the application of electron‐donor or electron‐acceptor difluoroalkylating reagents for the generation of CF₂FG and CF₂H radicals. Subsequent radical addition to substrates and additional organic transformations afford the corresponding difluoroalkylated derivatives. The present review describes the distinct strategies for the transition metal‐ and organic‐photocatalyzed difluoroalkylation of a broad range of organic substrates by visible light irradiation reported in the literature since 2014. magnified image

The present study aimed at identifying the neurophysiological responses associated with auditory stimulation during non-rapid eye movement (NREM) sleep using simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) recordings. It was reported earlier that auditory stimuli produce bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and NREM sleep. However, due to the spontaneous membrane potential fluctuations cortical responses may be highly variable during NREM. Here we now examine the modulation of cerebral responses to tones depending on the presence or absence of sleep spindles and the phase of the slow oscillation. Thirteen healthy young subjects were scanned successfully during stage 2–4 NREM sleep in the first half of the night in a 3 T scanner. Subjects were not sleep-deprived and sounds were post hoc classified according to (i) the presence of sleep spindles or (ii) the phase of the slow oscillation during (±300 ms) tone delivery. These detected sounds were then entered as regressors of interest in fMRI analyses. Interestingly wake-like responses – although somewhat altered in size and location – persisted during NREM sleep, except during present spindles (as previously published in Dang-Vu et al., 2011) and the negative going phase of the slow oscillation during which responses became less consistent or even absent. While the phase of the slow oscillation did not alter brain responses in primary sensory cortex, it did modulate responses at higher cortical levels. In addition EEG analyses show a distinct N550 response to tones during the presence of light sleep spindles and suggest that in deep NREM sleep the brain is more responsive during the positive going slope of the slow oscillation. The presence of short temporal windows during which the brain is open to external stimuli is consistent with the fact that even during deep sleep meaningful events can be detected. Altogether, our results emphasize the notion that spontaneous fluctuations of brain activity profoundly modify brain responses to external information across all behavioral states, including deep NREM sleep.

The widespread use of β-lactam antibiotics has led to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to β-lactams by two main mechanisms: the production of β-lactamases, sometimes accompanied by a decrease of outer membrane permeability, and the production of low-affinity, drug resistant Penicillin Binding Proteins (PBPs). PBPs remain attractive targets for developing new antibiotic agents because they catalyse the last steps of the biosynthesis of peptidoglycan, which is unique to bacteria, and lies outside the cytoplasmic membrane. Here we summarize the “current state of the art” of non-β-lactam inhibitors of PBPs, which have being developed in an attempt to counter the emergence of β-lactam resistance. These molecules are not susceptible to hydrolysis by β-lactamases and thus present a real alternative to β-lactams. We present transition state analogs such as boronic acids, which can covalently bind to the active serine residue in the catalytic site. Molecules containing ring structures different from the β-lactam-ring like lactivicin are able to acylate the active serine residue. High throughput screening methods, in combination with virtual screening methods and structure based design, have allowed the development of new molecules. Some of these novel inhibitors are active against major pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and thus open avenues new for the discovery of novel antibiotics.

Despite a growing interest in CHF₂ in medicinal chemistry, there is a lack of efficient methods for the insertion of CHF¹⁸F into druglike compounds. Herein described is a photoredox flow reaction for ¹⁸F‐difluoromethylation of N‐heteroaromatics that are widely used in medicinal chemistry. Following the two‐step synthesis for a new ¹⁸F‐difluoromethylation reagent, the photoredox reaction is completed within two minutes and proceeds by C−H activation, circumventing the need for pre‐functionalization of the substrate. The method is operationally simple and affords straightforward access to radiolabeled N‐heteroaromatics with high molar activity suitable for biological in vivo studies and clinical application.

Aptamers provide a potential source of alternative targeting molecules for existing antibody diagnostics and therapeutics. In this work, we selected novel DNA aptamers targeting the HER2 receptor by an adherent whole-cell SELEX approach. Individual aptamers were identified by next generation sequencing and bioinformatics analysis. Two aptamers, HeA2_1 and HeA2_3, were shown to bind the HER2 protein with affinities in the nanomolar range. In addition, both aptamers were able to bind with high specificity to HER2-overexpressing cells and HER2-positive tumor tissue samples. Furthermore, we demonstrated that aptamer HeA2_3 is being internalized into cancer cells and has an inhibitory effect on cancer cell growth and viability. In the end, we selected novel DNA aptamers with great potential for the diagnosis and possible treatment of HER2-positive cancer.