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Scientific discoveries often start with an observation that does not quite make sense, within the framework of a well-established hypothesis. It is when researchers delve deeply to understand such perplexing data that established hypotheses are modified or replaced, and new and expanded knowledge of the system can be gained. This is often the case in the field of drug discovery. In this Perspective, case studies demonstrate how an understanding of perplexing data can lead to novel discoveries regarding the biological function of drug targets, or the mechanisms of compound-target interactions, that can ultimately result in new drugs entering the clinic. These case studies reinforce two interdependent themes (1) that understanding the pathophysiological context in which drug targets function and the mechanistic details of drug-target interactions are critical to efficient and effective drug discovery and (2) that investing time and energy into following up on perplexing data can lead to novel discoveries that can drive the development of new and improved medicines.A tetraimidazole-decorating tetraphenylpyrazine has been designed and utilized for the fabrication of a novel metal-organic framework (MOF), denoted as Mn(Tipp)(A)2n·2H2O (TippMn, where Tipp = 2,3,5,6-tetrakis[4-[(1H-imidazol-1-yl)methyl]phenyl]pyrazine and A = deprotonation of 1,4-naphthalenedicarboxylic acid), through hydrothermal synthesis. Structural analysis reveals that TippMn possesses a 2-fold-interpenetrated 4,8-connected three-dimensional (3D) network with an unprecedented 416·61244·62 topology. Fluorescent spectral investigations indicate that TippMn shows discriminative fluorescence when treated by Cr3+ and Cu2+, giving an INHIBIT logical gate performance. Meanwhile, TippMn can be further used as a sensor for MnO4- and 2,4,6-trinitrophenol (TNP) by fluorescence quenching. Notably, the sensing processes toward Cu2+, Cr3+, MnO4-, and TNP are labeled with high selectivity and sensitivity, quick response, and good recyclability. It is anticipated that this MOF-based versatile sensor could shed light on the exploration of MOFs for fluorescent sensors, optical switches, etc.[Cu(bipy)(C6F5)] reacts with most aryl iodides to form heterobiphenyls by cross-coupling, but when Rf-I is used (Rf = 3,5-dicholoro-2,4,6-trifluorophenyl), homocoupling products are also formed. Kinetic studies suggest that, for the homocoupling reaction, a mechanism based on transmetalation from [Cu(bipy)(C6F5)] to Cu(III) intermediates formed in the oxidative addition step is at work. Density functional theory calculations show that the interaction between these Cu(III) species and the starting Cu(I) complex involves a Cu(I)-Cu(III) electron transfer concerted with the formation of an iodine bridge between the metals and that a fast transmetalation takes place in a dimer in a triplet state between two Cu(II) units.The oxygen evolution reaction (OER) plays a paramount role in a variety of electrochemical energy conversion devices, and the exploration of highly active, stable, and low-cost electrocatalysts is one of the most important topics in this field. The exfoliated black phosphorus (EBP) nanosheet with a two-dimensional (2D) layered structure has high carrier mobility but is limited by excessive oxygen-containing intermediate absorption and fast deterioration in air. We here report the fabrication of nanohybrids of amorphous CoFeB nanosheets on EBP nanosheets (EBP/CoFeB). The 2D/2D heterostructure, thanks to the electronic interactions and oxygen affinity difference between EBP and CoFeB nanosheets, is capable of balancing the oxygen-containing intermediate absorption to an optimal status for facilitating the OER process. While the crystalline EBP contributes to the improved conductivity, the amorphous coating protects EBP and thus ensures the catalytic stability. The EBP/CoFeB electrocatalyst shows excellent OER performance with an ultralow overpotential of 227 mV at 10 mA cm-2 with an ultrasmall Tafel slope of 36.7 mV dec-1 with excellent stability. This study may inspire more researches to develop heterostructured nanohybrid electrocatalysts for a diversity of electrochemical reactions.A Pd-catalyzed difluoroalkylation/cyclization/phosphinoylation of 2-vinyloxy arylalkynes with ethyl difluoroiodoacetate and diarylphosphine oxides has been successfully developed. This reaction allows the formation of Csp3-CF2, Csp3-Csp2, and Csp2-P(O) bonds in one step, providing a straightforward route to difluoroalkyl-containing tetrasubstituted alkenylphosphine oxides with complete stereoselectivities under mild conditions.The stereoselective and divergent synthesis of two aza-nucleosides is reported. Starting from xylofuranose 9, aza-adenosine 2 was prepared in 13 steps and 7% overall yield, and aza-guanosine 3 was prepared in 13 steps and 7.8% overall yield. Compared to the original syntheses, some advantages of these new routes are significant yield improvement, overall step-count reduction, an optimized protecting group strategy, the development of a versatile platform for nitrogenous base incorporation, and the elimination of hazardous reagents (e.g., benzyl isocyanate, Et3N·HF).Ultrafast two-dimensional infrared (2D IR) spectroscopy and Fourier transform infrared (FTIR) spectroscopy are often performed in tandem, with FTIR typically used to interpret and provide hypotheses for 2D IR experiments. Comparisons between 2D IR and FTIR spectra can also be used to examine the structure and orientation in systems of coupled vibrational chromophores. The most common method for comparing 2D IR and FTIR lineshapes, the diagonal slice method, contains significant artifacts when applied to oscillators with low anharmonicities. Here, we introduce a new technique, the pump slice amplitude (PSA) method, for relating 2D IR lineshapes to FTIR lineshapes and compare PSAs against diagonal slices using theoretical and experimental spectra. We find that PSAs are significantly more similar to FTIR lineshapes than diagonal slices in systems with low anharmonicity.The influence of some enological parameters on pyrrole concentrations in Chardonnay wines was studied. Osimertinib purchase First, a quantitative method to assay five pyrroles was optimized and applied to determine their content in wines produced in different containers. All pyrroles were observed in wines aged in a stainless-steel tank, which indicated that they have a varietal or fermentative origin. However, their concentrations were significantly higher in wines made in new barrels than in older barrels or in a stainless-steel tank, so oak wood may largely contribute during the winemaking process. A quantitative method to assay pyrroles in oak wood extract was also developed to study the influence of several cooperage parameters such as different types of traditional toasting, as well as the temperature and the time of toasting. Significant differences were observed on pyrrole concentrations in oak wood extracts according to these different cooperage parameters. These findings bring new perspectives to the monitoring of winemaking and the aging of Chardonnay wines.