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Treatment of the complexes [Re(NO)2(PR3)2][BAr(F)4] (R = Cy, 1 a; R = iPr, 1 b) with phenyldiazomethane gave the cationic benzylidene species [Re{CH(C6H5)}(NO)2(PR3)2][BAr(F)4] (2 a and 2 b) in good yields. Upon reaction of 2 a and 2 b with acetonitrile, the consecutive formation of [Re(N[triple bond]CCH3)(N[triple bond]CPh)(NO)(OC(CH3)=NH)(PR3)][BAr(F)4] (3 a and 3 b) and [Re(NCCH3)(OC{CH3}NH{C6H5})(NO)(PR3)2][BAr(F)4] (4 a and 4 b) was observed. The proposed reaction sequence involves the coupling of coordinated NO, carbene and acetonitrile molecules to yield the (1Z)-N-[imino(phenyl)methyl]ethanimidate ligand. The coupling of the nitrosyl and the benzylidene is anticipated to occur first, forming an oximate species. The subsequent acetonitrile addition can be envisaged as a heteroene reaction of the oximate and the acetonitrile ligand yielding 3 a and 3 b, which in turn can cyclise and undergo a prototropic shift initiated by an internal attack of the ethaneimidate ligand on the benzonitrile moiety to afford 4 a and 4 b.

The addition of an excess of phenyldiazomethane to chlorobenzene solutions of the cationic dinitrosyl bisphosphine rhenium(-I) complexes [Re(NO)2(PR3)2][BAr(F)4] (R = Cy 1a, R = (i)Pr 1b) gave the corresponding benzylidene complexes [Re{=CH(C6H5)}(NO)2(PR3)2][BAr(F)4] (2a and 2b) in good yields. The treatment of 2b with dioxygen resulted in the oxidation of one of the nitrosyl ligands into the corresponding eta2-nitrito (3b) and nitrato complexes (4b) both in the solid state and in solution. In the case of the tricyclohexylphosphine derivative 2a the analogous conversion was not observed. A mechanism for the reaction of 2b with O2 is proposed which is based on an initial SET to the O2 molecule and subsequent formation of a peroxynitrite complex followed by the formation of a dinuclear mU-N2O4 intermediate. This in turn would undergo fission of the peroxo bond to afford 3b. A related sequence of steps is anticipated for the transformation of 3b to 4b. Furthermore, a similar mechanism seems reasonable for the seemingly topochemical reaction of 2b to 3b and 4b in the solid state. The initial SET to dioxygen and subsequent formation of the peroxynitrite complex is supported by DFT calculations on the trimethylphosphine model complexes [Re=CH{C6H5})(NO)2(PMe3)2]n+ (n = 1 and 2).

The discovery of novel drugs against animal parasites is in high demand due to drug-resistance problems encountered around the world. Herein, the synthesis and characterization of 27 organic and organometallic derivatives of the recently launched nematocidal drug monepantel (Zolvix® ) are described. The compounds were isolated as racemates and were characterized by 1 H, 13 C, and 19 F NMR spectroscopy, mass spectrometry, and IR spectroscopy, and their purity was verified by microanalysis. The molecular structures of nine compounds were confirmed by X-ray crystallography. The anthelmintic activity of the newly designed analogues was evaluated in vitro against the economically important parasites Haemonchus contortus and Trichostrongylus colubriformis. Moderate nematocidal activity was observed for nine of the 27 compounds. Three compounds were confirmed as potentiators of a known monepantel target, the ACR-23 ion channel. Production of reactive oxygen species may confer secondary activity to the organometallic analogues. Two compounds, namely, an organic precursor (3 a) and a cymantrene analogue (9 a), showed activities against microfilariae of Dirofilaria immitis in the low microgram per milliliter range.

Item does not contain fulltext, Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.

The asymmetric unit of the title compound, C(17)H(13)N(4)(+)center dot BF(4) , contains one half of the benzimidazolium cation and one half of the tetrafluoridoborate anion, with crystallographic mirror planes bisecting the molecules. One F atom of the tetrafluoridoborate is equally disordered about a crystallographic mirror plane. In the crystal, C-H center dot center dot center dot F interactions link the cations and anions into layers parallel to (100). The crystal packing is further stabilized by F center dot center dot center dot pi contacts involving the tetrafluoridoborate anions and the five-membered rings F center dot center dot center dot centroid = 2.811 (2) angstrom].

In the title paramagnetic 19-electron neutral complex, W(BH(4))(C(21)H(24)N(2))(2)(NO)(2)], the W(0) atom is coordinated by two 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) carbene ligands, two NO groups and two H atoms of an eta(2)-tetrahydroborate ligand. Depending on the number of coordination sites (n) assigned to the BH4(-) ligand, the coordination geometry of the W atom may either be described as approximately trigonal-bipyramidal (n = 1) or as very distorted octahedral with the bridging H atoms filling two coordination positions (n = 2). In the latter case, the coplanar NO groups and bridging H atoms (r.m.s. deviation = 0.032 angstrom) form one octahedral plane, with mutually trans-oriented carbene ligands. In the crystal, molecules are connected via C-H center dot center dot center dot O interactions.

In the crystal structure of the title compound, [WCl2(NO)(C6H16P2)2]Cl, the seven-coordinated tungsten(II) center displays a distorted pentagonal-bipyramidal geometry with trans nitrosyl and chloride ligands. The NO and Cl ligands are disordered over two positions; the site occupancy factors are 0.6 and 0.4.

Cilia and flagella play important roles in many physiological processes, including cell and fluid movement, sensory perception, and development [1]. The biogenesis and maintenance of cilia depend on intraflagellar transport (IFT), a motility process that operates bidirectionally along the ciliary axoneme [1, 2]. Disruption in IFT and cilia function causes several human disorders, including polycystic kidneys, retinal dystrophy, neurosensory impairment, and Bardet-Bledl syndrome (BBS) [3-5]. To uncover new ciliary components, including IFT proteins, we compared C. elegans ciliated neuronal and nonciliated cells through serial analysis of gene expression (SAGE) and screened for genes potentially regulated by the cillogenic transcription factor, DAF-19 [6]. Using these complementary approaches, we identified numerous candidate ciliary genes and confirmed the ciliated-cell-specific expression of 14 novel genes. One of these, C27H5.7a, encodes a ciliary protein that undergoes IFT. As with other IFT proteins, its ciliary localization and transport is disrupted by mutations in IFT and bbs genes. Furthermore, we demonstrate that the ciliary structural defect of C. elegans dyf-13(mn396) mutants is caused by a mutation in C27H5.7a. Together, our findings help define a ciliary transcriptome and suggest that DYF-13, an evolutionarily conserved protein, is a novel core IFT component required for cilia function.