Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family play major regulatory roles in many cellular processes including DNA-processing and repair, proliferation, cytoskeleton dynamics, vesicular trafficking, apoptosis, and cell differentiation. As a consequence of cellular stress conditions, interaction of CK1 with the mitotic spindle is manifold increased pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is able to alter the activity of key proteins in signal transduction and signal integration molecules. In line with this notion, CK1 is tightly connected to the regulation and degradation of β-catenin, p53, and MDM2. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions, it is not surprising that mutations and alterations in the expression and/or activity of CK1 isoforms are often detected in various tumor entities including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer, adenocarcinomas of the pancreas, and ovarian cancer. Therefore, scientific effort has enormously increased (i) to understand the regulation of CK1 and its involvement in tumorigenesis- and tumor progression-related signal transduction pathways and (ii) to develop CK1-specific inhibitors for the use in personalized therapy concepts. In this review, we summarize the current knowledge regarding CK1 regulation, function, and interaction with cellular proteins playing central roles in cellular stress-responses and carcinogenesis.

[3]-Radialene-based dopant CN6-CP studied herein, with its reduction potential of +0.8 versus Fc/Fc+ and the lowest unoccupied molecular orbital level of -5.87 eV, is the strongest molecular p-dopant reported in the open literature, so far. The efficient p-doping of the donor-acceptor dithienyl-diketopyrrolopyrrole-based copolymer having the highest unoccupied molecular orbital level of -5.49 eV is achieved. The doped films exhibit electrical conductivities up to 70 S cm(-1) .

Herein we present a molecular doping of a high mobility diketopyrrolopyrrole−dithienylthieno[3,2-b]thiophene donor−acceptor copolymer poly[3,6-thiophene], PDPP(6-DO) 2 TT, with the electron-deficient compound hexafluorotetracyanonaphthoquinodimethane (F6TCNNQ). Despite a slightly negative HOMO donor −LUMO acceptor offset of −0.12 eV which may suggest a reduced driving force for the charge transfer (CT), a partial charge CT was experimentally observed in PDPP(6-DO) 2 TT:F6TCNNQ by absorption, vibrational, and electron paramagnetic resonance spectroscopies and predicted by density functional theory calculations. Despite the modest CT, PDPP(6-DO) 2 TT:F6TCNNQ films possess unexpectedly high conductivities up to 2 S/cm (comparable with the conductivities of the benchmark doped polymer system P3HT:F4TCNQ having a large positive offset). The observation of the high conductivity in doped PDPP(6-DO) 2 TT films can be explained by a high hole mobility in PDPP(6-DO) 2 TT blends which compensates a lowered (relatively to P3HT:F4TCNQ) concentration of free charge carriers. We also show that F6TCNNQ-doped P3HT, the system which has not been reported so far to the best of our knowledge, exhibits a conductivity up to 7 S/cm, which exceeds the conductivity of the benchmark P3HT:F4TCNQ system.

Members of the highly conserved pleiotropic CK1 family of serine/threonine-specific kinases are tightly regulated in the cell and play crucial regulatory roles in multiple cellular processes from protozoa to human. Since their dysregulation as well as mutations within their coding regions contribute to the development of various different pathologies, including cancer and neurodegenerative diseases, they have become interesting new drug targets within the last decade. However, to develop optimized CK1 isoform-specific therapeutics in personalized therapy concepts, a detailed knowledge of the regulation and functions of the different CK1 isoforms, their various splice variants and orthologs is mandatory. In this review we will focus on the stressinduced CK1 isoform delta (CK1δ), thereby addressing its regulation, physiological functions, the consequences of its deregulation for the development and progression of diseases, and its potential as therapeutic drug target.

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Strobilurin fungicides play a crucial role in protecting plants against different pathogens and securing food supplies. A series of 1,2,3-thiadiazole and thiazole-based strobilurins were rationally designed, synthesized, characterized, and tested against various fungi. Introduction of 1,2,3-thiadiazole greatly improved the fungicidal activity of the target molecules. Compounds 8a, 8c, 8d, and 10i exhibited a relatively broad spectrum of fungicidal activity. Compound 8a showed excellent activities against Gibberella zeae, Sclerotinia sclerotiorum, and Rhizoctonia cerealis with median effective concentrations (EC) of 2.68, 0.44, and 0.01 μg/mL, respectively; it was much more active than positive controls enestroburin, kresoxim-methyl, and azoxystrobin with EC between 0.06 and 15.12 μg/mL. Comparable or better fungicidal efficacy of compound 8a compared with azoxystrobin and trifloxystrobin against Sphaerotheca fuliginea and Pseudoperonspera cubensis was validated in cucumber fields at the same application dosages. Therefore, compound 8a is a promising fungicidal candidate worthy of further development.

Density functional (B3LYP/6-311+G) and ab initio (MP2/6-311+G and MP4(SDTQ)/6-311+G//MP2/6-311+G) calculations on the ring closure reactions of (E)- and Z-iminodiazomethane ((E)-5, (Z)--5), vinyldiazomethane 7, and formyldiazomethane 9 to 1H-1,2,3-triazole 6, 3H-pyrazole 8, and 1,2,3-oxadiazole 10, respectively, are reported. (E)-5 cyclizes via a low barrier (ca. 10 kcal mol(-)(1)) pseudopericyclic nonrotatory transition state. Ring closure of (Z)-5 and 7 proceeds by a monorotatory movement of the imino or vinyl group with a substantially higher barrier (ca. 25 kcal mol(-)(1)). Despite being endothermic, for the reaction 9 --> 10 also a rather low activation energy (ca. 10 kcal mol(-)(1)) is computed. The NBO analysis is used to interpret the electronic structures of the respective transition states in terms of their pericyclic monorotatory (TS ((Z)-5 --> 6), (TS (7 --> 8)) or pseudopericyclic nonrotatory ((TS ((E)-5 --> 6), (TS (9 --> 10)) nature.

The N-type semiconducting polymer, P(NDI2OD-T2), with different molecular weights (MW=23, 72, and 250 kg/mol) was used for the fabrication of field-effect transistors (FETs) with different semiconductor layer thicknesses. FETs with semiconductor layer thicknesses from ∼15 to 50 nm exhibit similar electron mobilities (μ's) of 0.2-0.45 cm2 V(-1) s(-1). Reduction of the active film thickness led to decreased μ values; however, FETs with ∼2 and ∼5 nm thick P(NDI2OD-T2) films still exhibit substantial μ's of 0.01-0.02 and ∼10(-4) cm2 V(-1) s(-1), respectively. Interestingly, the lowest molecular weight sample (P-23, MW≈23 kg/mol, polydispersity index (PDI)=1.9) exhibited higher μ than the highest molecular weight sample (P-250, MW≈250 kg/mol, PDI=2.3) measured for thicker devices (15-50 nm). This is rather unusual behavior because typically charge carrier mobility increases with MW where improved grain-to-grain connectivity usually enhances transport events. We attribute this result to the high crystallinity of the lowest MW sample, as confirmed by differential scanning calorimetry and X-ray diffraction studies, which may (over)compensate for other effects.