Activation of Nucleotide-Binding Oligomerization Domain 1 (NOD1) Receptor Signaling in Labeo rohita by iE-DAP and Identification of Ligand-Binding Key Motifs in NOD1 by Molecular Modeling and Docking

The nucleotide-binding oligomerization domain 1 (NOD1) receptor recognizes various pattern-associated structures of microbes through its leucine-rich repeat (LRR) domain and activates signaling cascades to induce innate immunity. This report describes the activation of NOD1 receptor signaling by gamma-d-glutamyl-meso-diaminopimelic acid (or γ-D-Glu-mDAP [iE-DAP]) in a commercially important fish species, rohu (Labeo rohita). It also described critical motifs in the NOD1-LRR domain that could be involved in binding iE-DAP, lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly I:C). The activation of NOD1 receptor signaling was studied by injecting iE-DAP, and analysis of tissue samples for NOD1 and receptor-interacting serine/threonine kinase (RICK) expression was done by quantitative real-time polymerase chain reaction (qRT-PCR) assay. To identify ligand-binding motifs in NOD1, the 3D model of NOD1-LRR was generated, followed by a 6-ns molecular dynamics simulation. Molecular docking of LPS with NOD1-LRR was executed at the Hex and PatchDock servers, and iE-DAP and poly I:C in the AutoDock 4.2, FlexX 2.1, Glide 5.5, and GOLD 4.1 programs. The results of qRT-PCR revealed significant (p?<?0.05) upregulation of NOD1 and RICK expression. Molecular docking revealed that the amino acid residues at LRR1–2, LRR3–7, and LRR8–9 could be involved in poly I:C, LPS, and iE-DAP binding, respectively. In fish, this is the first report describing the 3D structure of NOD1-LRR and its critical ligand-binding motifs.     

Stereoselective Seed-Induced Living Supramolecular Polymerization

Stereoselective and temporally controlled supramolecular polymerizations are ubiquitous in nature and are desirable attributes for the design of chiral, well-defined functional materials. Kinetically controlled, living supramolecular polymerization (LSP) has emerged recently for the synthesis of supramolecular polymers with controlled length and narrow dispersity. On the other hand, stringent design requirements for chiral-discriminating monomers precludes the stereoselective control of the supramolecular polymer structure. Herein, a synergetic stereo- and structural control of supramolecular polymerization by the realization of an unprecedented stereoselective seed-induced LSP is reported. Homochiral and seeded growth is demonstrated with bischromophoric naphthalene diimide (NDI) enantiomers with a chiral binaphthyl amine core, exhibiting strong self-recognition abilities and pathway complexity.     

Ritter-enabled catalytic asymmetric chloroamidation of olefins

Intermolecular asymmetric haloamination reactions are challenging due to the inherently high halenium affinity (HalA) of the nitrogen atom, which often leads to N-halogenated products as a kinetic trap. To circumvent this issue, acetonitrile, possessing a low HalA, was used as the nucleophile in the catalytic asymmetric Ritter-type chloroamidation of allyl-amides. This method is compatible with Z and E alkenes with both alkyl and aromatic substitution. Mild acidic workup reveals the 1,2-chloroamide products with enantiomeric excess greater than 95% for many examples. We also report the successful use of the sulfonamide chlorenium reagent dichloramine-T in this chlorenium-initiated catalytic asymmetric Ritter-type reaction. Facile modifications lead to chiral imidazoline, guanidine, and orthogonally protected 1,2,3 chiral tri-amines.

Intermolecular haloamination reactions are challenging due to the high halenium affinity of the nitrogen atom. This is circumvented by using acetonitrile as an attenuated nucleophile, resulting in an enantioselective halo-Ritter reaction.     

Dioxomolybdenum(VI) and dioxotungsten(VI) complexes supported by an amido ligand

Stepwise addition of one equivalent of n-butyllithium and trimethylsilyl chloride to 2-tert-butylmercaptoaniline affords the new ligand 1-(Me3SiNH)-2-(t-BuS)C6H4 (LH), that reacts with one equivalent of butyllithium to its lithium salt LLi. Dioxodichloromolybdenum [MoO2Cl2] and dioxodichlorotungsten dimethoxyethane [WO2Cl2(dme)] react in tetrahydrofuran solution at low temperature with two equivalents LLi to monomeric dioxomolybdenum(VI) [MoO2L2] (1) and dioxotungsten(VI) complex [WO2L2] (2) employing two bidentate amido thioether ligands. The crystallographic determination of the molecular structures of 1 and 2 show evidence for M...S contacts. The reaction of [MoO2Cl2] with LLi in tetrahydrofuran solution at room temperature leads next to 1 to two compounds where silyl group migration from nitrogen to oxygen atoms occurs forming [Mo(=NL')2(OSiMe)2] (3) and [Mo(=NL')2(OSiMe3)L] (4, L' = N-2-t-BuSC6H4) as determined by NMR spectroscopy. Compound 4 was isolated in low yield and its molecular structure determined by X-ray crystallography. Higher yields of a bisimido complex can be obtained by the direct reaction of one equivalent of LLi with [Mo(NAr)2Cl2(dme)] (Ar = 2,6-Me2C6H4) forming [Mo(NAr)2LCl] (5).     

A reactivity change of a strontium monohydroxide by umpolung to an acid

Controlled hydrolysis of strontium amide LSrN(SiMe 3) 2(thf) (L = CH(CMe2,6- i-Pr 2C 6H 3N) 2) ( 1) gave an unprecedented example of a hydrocarbon-soluble strontium hydroxide, [LSr(thf)(mu-OH) 2Sr(thf) 2L] ( 2). In compound 2, the tetrahydrofuran (THF) molecules can easily replaced by benzophenone and triphenylphosphine oxide to yield [LSr(mu-OH)(OCPh 2)] 2 ( 3) and [LSr(mu-OH)(OPPh 3)] 2 ( 4) compounds. Among the two strontium atoms of 2, one is coordinated to a single THF molecule, while the other is coordinated to two THF molecules. Interestingly, strontium hydroxide complex 2 behaves as an acid in its reaction with Zr(NMe 2) 4 and results in a heterobimetallic oxide, [LSr(mu-O)Zr(NMe 2) 3] 2 ( 5). Compound 5 is dimeric in the solid state and contains a Sr 2Zr 2O 2 core.     

Synthesis, structural characterization, catalytic properties, and theoretical study of compounds containing an Al-O-M (M = Ti, Hf) core

Two single oxygen-bridged heterobimetallic oxides of Al(III) with group 4 metals (Ti, Hf) have been prepared. The reaction of LAlMeOH (1) [L = CH(N(Ar)(CMe))2, Ar = 2,6-iPr2C6H3] with dimethylmetallocenes of Ti and Hf in toluene (80 degrees C) and ether (room temperature), respectively, resulted in the formation of LAl(Me)(mu-O)M(Me)Cp2 [M = Ti (2), Hf (3)] in moderate to good yield. Compounds 2 and 3 were characterized by elemental analysis, IR, NMR (1H and 13C), EI-MS, and single-crystal X-ray structural analysis. Furthermore, compound 2 showed good catalytic activity in ethylene and styrene homopolymerization, while compound 3 is less active in ethylene polymerization. The styrene polymerization yields atactic polystyrene.     

A phenomenological approach to modeling chemical dynamics in nonlinear and two-dimensional spectroscopy

We present an approach for calculating nonlinear spectroscopic observables, which overcomes the approximations inherent to current phenomenological models without requiring the computational cost of performing molecular dynamics simulations. The trajectory mapping method uses the semi-classical approximation to linear and nonlinear response functions, and calculates spectra from trajectories of the system's transition frequencies and transition dipole moments. It rests on identifying dynamical variables important to the problem, treating the dynamics of these variables stochastically, and then generating correlated trajectories of spectroscopic quantities by mapping from the dynamical variables. This approach allows one to describe non-Gaussian dynamics, correlated dynamics between variables of the system, and nonlinear relationships between spectroscopic variables of the system and the bath such as non-Condon effects. We illustrate the approach by applying it to three examples that are often not adequately treated by existing analytical models--the non-Condon effect in the nonlinear infrared spectra of water, non-Gaussian dynamics inherent to strongly hydrogen bonded systems, and chemical exchange processes in barrier crossing reactions. The methods described are generally applicable to nonlinear spectroscopy throughout the optical, infrared and terahertz regions.     

Positron annihilation lifetime studies on La0.5Pb0.5Mn1−yCryO3

Concentration dependent positron annihilation lifetime (PAL) measurements on Cr doped La_0.5Pb_0.5Mn_1−yCr_yO₃ (y=0.075, 0.15, 0.3, 0.35, 0.45) samples showing metal-insulator transitions (MIT) between 178 and 276 K (depending on y) reveal anomalous variation of average and bulk PAL, τ_av and τ_B, respectively, around y=0.35. Such anomaly has not, however, been observed from the corresponding magnetic susceptibility and resistivity data. Interestingly, the model parameters (polaron radius, number of ion sites per unit volume) obtained from fitting the high temperature (above MIT, T_p) resistivity data with small polaron hopping model show the signature of the said anomaly around the same concentration. Nonlinear variations of τ_av and τ_B support the existence of small polarons (T>T_p) which act as defect centers in such rare-earth manganites. Analysis of X-ray diffraction pattern confirms a change of lattice parameters indicating a structural transformation from rhombohedral (for y≤0.30) to orthorhombic (for y≥0.35) in the present system.     

Syntheses, characterization, and X-ray crystal structures of beta-diketiminate group 13 hydrides, chlorides, and fluorides

A series of organometallic compounds of group 13 metals supported by the sterically encumbered beta-diketiminate ligand containing hydrides, fluorides, chlorides, and bromide have been synthesized and structurally characterized. The synthetic strategy applied utilizes halide metathesis and reduction of metal chlorides to the corresponding hydrides. Thus, the reaction of LLi.OEt2 with MeMCl2 affords LM(Me)Cl (M = Al (1), Ga (2), In (3)) and LGaBr2 (4) with GaBr3. Reduction of LGa(Me)Cl with LiH.BEt3 leads to the formation of LGa(Me)H (10). Synthesis of LGaH(2) (12) has been accomplished by reacting LGaI2 (8) with LiH.BEt3. LAl(Me)Cl (1) and LAlH2 (6) have been converted to LAl(Me)F (5) and LAlF2 (7), respectively. The former was obtained in a reaction of LAl(Me)Cl with Me3SnF while the latter was isolated in a reaction of LAlH2 with BF3.OEt2. Similarly reaction of LGaI2 (8) with Me3SnF affords LGaF2 (9). Compounds reported herein have been characterized by elemental analyses, IR, NMR, EI-MS, and single-crystal X-ray diffraction techniques.