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The title compound, C22H28N2O6, crystallizes with four half-molecules in the asymmetric unit: each molecule is located about a crystallographic inversion centre. The central methylene groups of two molecules are disordered over two sets of equally occupied sites. The crystal packing is characterized by sheets of molecules parallel to (114).
The central structural element of the title compound, C24H29NO2, is a carbazole unit substituted with two acetyl residues and an octyl chain. The acetyl residues are nearly coplanar [dihedral angles = 5.37 (14) and 1.0 (3)°] with the carbazole unit which is essentially planar (r.m.s. deviation for all non-H atoms = 0.025 Å). The octyl chain adopts an all-trans conformation. The crystal packing is stabilized by C—H ... O hydrogen bonds.
The title molecule, C34H28I4·4C6H6, has crystallographic 4 symmetry and crystallizes with four symmetry-related benzene solvent molecules. The phenyl group is eclipsed with one of the adamantane C—C bonds. The tetraphenyladamantane units and the benzene solvent molecules are connected by weak intermolecular phenyl–benzene C—H⋯π and benzene–benzene C—H⋯π interactions. In the crystal, molecules are linked along the c-axis direction via the iodophenyl groups by a combination of weak intermolecular I⋯I [3.944 (1) Å] and I⋯π(phenyl) [3.608 (6) and 3.692 (5) Å] interactions.
The dihydropyrimidine ring of the title compound, C13H15ClN2S, adopts an envelope conformation with five almost coplanar atoms (r.m.s. deviation = 0.054 Å) and the C atom bearing the two methyl substituents deviating from this plane by 0.441 (2) Å. The best plane through the five almost coplanar atoms forms a dihedral angle of 89.56 (5)° with the benzene ring. The crystal packing is characterized by centrosymmetric dimers connected by pairs of N—H ... S hydrogen bonds.
The title compound, C8H11FN5 +·Cl-, crystallized with a monoprotonated 1-(4-fluorophenyl)biguanidinium cation and a chloride anion in the asymmetric unit. The biguanidium group is not planar [dihedral angle between the two CN3 groups = 52.0 (1)°] and is rotated with respect to the phenyl group [tau = 54.3 (3)°]. In the crystal, N—H ... N hydrogen-bonded centrosymmetric dimers are connected into ribbons, which are further stabilized by N—H ... Cl interactions, forming a three-dimensional hydrogen-bonded network.
In the title compound, C11H11N3O2, the dihedral angle between the central ethanone fragment and the 4-methoxyphenyl group is 2.9 (2)°, while that between the ethanone fragment and the triazole ring is 83.4 (2)°. The dihedral angle between the planes of the triazole and benzene rings is 81.7 (1)°. The 4-methoxyphenyl group is cis with respect to the ethanone fragment O atom across the exocyclic C—C bond. In the crystal, molecules are linked by C—H ... N interactions into C(9) chains along [001].
We present here a set of 13C-direct detected NMR experiments to facilitate the resonance assignment of RNA oligonucleotides. Three experiments have been developed: (1) the (H)CC-TOCSY-experiment utilizing a virtual decoupling scheme to assign the intraresidual ribose 13C-spins, (2) the (H)CPC-experiment that correlates each phosphorus with the C40 nuclei of adjacent nucleotides via J(C,P) couplings and (3) the (H)CPC-CCH-TOCSY-experiment that correlates the phosphorus nuclei with the respective C10,H10 ribose signals. The experiments were applied to two RNA hairpin structures. The current set of 13C-direct detected experiments allows direct and unambiguous assignment of the majority of the hetero nuclei and the identification of the individual ribose moieties following their sequential assignment. Thus, 13C-direct detected NMR methods constitute useful complements to the conventional 1H-detected approach for the resonance assignment of oligonucleotides that is often hindered by the limited chemical shift dispersion. The developed methods can also be applied to large deuterated RNAs. Keywords: NMR spectroscopy , Direct carbon , detection , RNA
17-Acetoxymulinic acid
(2010)
The title compound, [systematic name: 5a-acetoxymethyl-3-isopropyl-8-methyl-1,2,3,3a,4,5,5a,6,7,10,10a,10b-dodecahydro-7,10-endo-epidioxycyclohepta[e]indene-3a-carboxylic acid], C22H32O6 (I), is closely related to methyl 5a-acetoxymethyl-3-isopropyl-8-methyl-1,2,3,3a,4,5,5a,6,7,10,10a,10b-dodecahydro-7,10-endo-epidioxycyclohepta[e]indene-3a-carboxylate, (II) [Brito et al., (2008 [triangle]). Acta Cryst. E64, o1209]. There are two molecules in the asymmetric unit, which are linked by two strong intramolecular O—H ... O hydrogen bonds with graph-set motif R 2 2(8). In both (I) and (II), the conformation of the three fused rings are almost identical. The five-membered ring has an envelope conformation, the six-membered ring has a chair conformation and the seven-membered ring has a boat conformation. The most obvious differences between the two compounds is the observed disorder of the acetoxymethyl fragments in both molecules of the asymmetric unit of (I). This disorder is not observed in (II). The crystal structure and the molecular conformation is stabilized by intermolecular C—H ... O hydrogen bonds. The ability to form hydrogen bonds is different in the two compounds. The crystal studied was a non-merohedral twin, the ratio of the twin components being 0.28 (1):0.72 (1)
In the title compound, C4H7N3O·C2H6OS, creatinine [2-amino-1-methyl-1H-imidazol-4(5H)one] exists in the amine form. The ring is planar (r.m.s. deviation for all non-H atoms = 0.017 Å). In the crystal, two creatinine molecules form centrosymmetric hydrogen-bonded dimers linked by pairs of N—H[cdots, three dots, centered]N hydrogen bonds. In addition, creatinine is linked to a dimethyl sulfoxide molecule by an N—H[cdots, three dots, centered]O interaction. The packing shows layers parallel to (120).
In the title compound, C27H19N3O4, the phenol and pyrazole rings are almost coplanar [dihedral angle = 0.95 (12)°] due to an intramolecular O—H ... N hydrogen bond, whereas the phenyl ring is tilted by 40.81 (7)° with respect to the plane of the pyrazole ring. The aromatic ring with a nitrophenoxy substituent makes a dihedral angle of 54.10 (7)° with the pyrazole ring.
4-Nitrophenyl 1-naphthoate
(2010)
In the title compound, C17H11NO4, the dihedral angle between the two benzene rings is 8.66 (3)°. The nitro group is twisted by 4.51 (9)° out of the plane of the aromatic ring to which it is attached. The presence of intermolecular C—H ... O contacts in the crystal structure leads to the formation of chains along the c axis.
The two rings in the title compound, C11H12N2O4S, are roughly coplanar [dihedral angle = 6.77 (8)°]. Whereas the two outer methyl groups of the three methoxy groups are almost coplanar with the aromatic ring to which they are attached [C—C—O—C torsion angles = 8.5 (3) and -8.3 (3)°], the methyl group of the central methoxy substituent is not [C—C—C—C = -78.4 (3)°]. The crystal packing is stabilized by N—H ... O hydrogen bonding.
Leukotrienes constitute a group of bioactive lipids generated by the 5-lipoxygenase (5-LO) pathway. An increasing body of evidence supports an acute role for 5-LO products already during the earliest stages of pancreatic, prostate, and colorectal carcinogenesis. Several pieces of experimental data form the basis for this hypothesis and suggest a correlation between 5-LO expression and tumor cell viability. First, several independent studies documented an overexpression of 5-LO in primary tumor cells as well as in established cancer cell lines. Second, addition of 5-LO products to cultured tumor cells also led to increased cell proliferation and activation of anti-apoptotic signaling pathways. 5-LO antisense technology approaches demonstrated impaired tumor cell growth due to reduction of 5-LO expression. Lastly, pharmacological inhibition of 5-LO potently suppressed tumor cell growth by inducing cell cycle arrest and triggering cell death via the intrinsic apoptotic pathway. However, the documented strong cytotoxic off-target effects of 5-LO inhibitors, in combination with the relatively high concentrations of 5-LO products needed to achieve mitogenic effects in cell culture assays, raise concern over the assignment of the cause, and question the relationship between 5-LO products and tumorigenesis. Keywords: leukotriene, apoptosis, cell proliferation, mitogenic effects, cytotoxicity
9-Bromo-9-borafluorene
(2010)
The title compound, C12H8BBr, crystallizes with three essentially planar molecules (r.m.s. deviations = 0.018, 0.020 and 0.021Å) in the asymmetric unit: since the title compound is rigid, there are no conformational differences between these three molecules. The crystal packing resembles a herringbone pattern.
[Nachruf] Walter Wetzel
(2010)
Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5'-end) and complementary sequences in the 3'UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low.
In the crystal of the title compound [systematic name: 2-(3,5-diamino-6-chloropyrazin-2-ylcarbonyl)guanidinium chloride methanol disolvate], C6H9ClN7O+·Cl-·2CH3OH , the components are connected by N—H ... N, N—H ... Cl, N—H ... O, O—H ... Cl and O—H ... O hydrogen bonds into a three-dimensional network. The dihedral angle between the aromatic ring and the guanidine residue is 6.0 (2)°.
The thermodynamics of base pairing is of fundamental importance. Fluorinated base analogs are valuable tools for investigating pairing interactions. To understand the influence of direct base–base interactions in relation to the role of water, pairing free energies between natural nucleobases and fluorinated analogs are estimated by potential of mean force calculations. Compared to pairing of AU and GC, pairing involving fluorinated analogs is unfavorable by 0.5–1.0 kcal mol -1. Decomposing the pairing free energies into enthalpic and entropic contributions reveals fundamental differences for Watson–Crick pairs compared to pairs involving fluorinated analogs. These differences originate from direct base–base interactions and contributions of water. Pairing free energies of fluorinated base analogs with natural bases are less unfavorable by 0.5–1.0 kcal mol -1 compared to non-fluorinated analogs. This is attributed to stabilizing C–F…H–N dipolar interactions and stronger N…H–C hydrogen bonds, demonstrating direct and indirect influences of fluorine. 7-methyl-7H-purine and its 9-deaza analog (Z) have been suggested as members of a new class of non-fluorinated base analogs. Z is found to be the least destabilizing universal base in the context of RNA known to date. This is the first experimental evidence for nitrogen-containing heterocylces as bioisosteres of aromatic rings bearing fluorine atoms.