The discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O 2 as a green oxidant. The C-H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2′-deoxy-5-difluoromethyluridine (F 2 TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery.

Herein, we present a novel label-free fluorescent assay for monitoring the activity and inhibition of protein kinases based on the aggregation behavior of unmodified CdTe quantum dots (QDs). In this assay, cationic substrate peptides induce the selective aggregation of unmodified QDs with anionic surface charge, whereas phosphorylated peptides do not. Phosphorylation by kinase alters the net charge of peptides and subsequently inhibits the aggregation of unmodified QDs, causing an enhanced fluorescence with a 45 nm blue-shift in emission and a yellow-to-green emission color change. Hence the fluorescence response allows this QD-based method to easily probe kinase activity by a spectrometer or even by the naked eye. The feasibility of the method has been demonstrated by sensitive measurement of the activity of cAMP-dependent protein kinase (PKA) with a low detection limit (0.47 mU μL(-1)). On the basis of the fluorescence response of QDs on the concentration of PKA inhibitor H-89, the IC(50) value, the half maximal inhibitory concentration, was estimated, which was in agreement with the literature value. Moreover, the system can be applicable to detect the Forskolin/3-isobutyl-1-methylxantine (IBMX)-stimulated activation of PKA in cell lysate. Unlike the existing QD-based enzyme activity assays in which the modification process of QDs is essential, this method relies on unmodified QDs without the requirement of peptide labeling and QDs' modification, presenting a promising candidate for cost-effective kinase activity and inhibitor screening assays.

A new label-free method for the detection of apoptosis was proposed based on colorimetric assay of caspase-3 activity using an unlabeled Asp-Glu-Val-Asp (DEVD)-containing peptide substrate and unmodified gold nanoparticles (AuNPs).

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A ring-opening C(sp3)–C coupling of cyclobutanone oxime esters for the preparation of cyanoalkyl containing heterocycles was realized under visible-light or sunlight irradiation.

A novel, sensitive, nonenzymatic amperometric sensor for the reliable detection of extracellular H 2 O 2 released from living cells was fabricated based on Fe 3 O 4 /reduced graphene oxide (Fe 3 O 4 /rGO) nanocomposites, which were prepared using a simple and cost-effective one-pot approach. Electrochemical performances of the Fe 3 O 4 /rGO nanocomposites modified glassy carbon electrode (GCE) were studied. The results demonstrated that this H 2 O 2 sensor exhibited excellent electrocatalytic performance towards the reduction of H 2 O 2 at a potential of À0.3 V in the wide linear concentration range from 0.001 to 20 mM with a high sensitivity of 387.6 mA mM À1 cm À2 and a detection limit as low as 0.17 mM (S/N ¼ 3), which was lower than certain enzymes and noble metal nanomaterials-based biosensors. Moreover, good anti-interference property, reproducibility, and long-term stability of the enzymeless sensor were achieved. Because of these remarkable analytical advantages, a novel, effective approach for the detection of extracellular H 2 O 2 released from HeLa cells stimulated by CdTe quantum dots (QDs) was established by the constructed sensor. Since H 2 O 2 is a byproduct of several oxidative biological reactions, this work could be applied to study the downstream biological effects of various stimuli in pathophysiology, and may expand the application of Fe 3 O 4 -based nanomaterials in the field of electrochemical sensing and bioanalysis.

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