The structure and chemistry of tris(pentafluorophenyl)borane protected mononuclear nitridotitanium complexes

Treatment of TiCl(NMe(2))(3) with H(3)N·B(C(6)F(5))(3) results in N-H activation and ligand exchange to yield the structurally characterised salt [TiCl(NMe(2))(2)(NMe(2)H)(2)](+)[Ti[triple bond]NB(C(6)F(5))(3)(Cl)(2)(NMe(2)H)(2)](-). Cation exchange with [Me(4)N]Cl, [Ph(4)P]Cl and [(PhCH(2))Ph(3)P]Cl yields the respective ammonium and phosphonium salts of the [Ti[triple bond]NB(C(6)F(5))(3)(Cl)(2)(NMe(2)H)(2)](-) anion. X-ray crystallography reveals that the essential trigonal bipyramidal geometry and composition of the anion is retained in each of these salts despite some minor variations in the Ti-N-B angle and the nature of the interionic interactions. Electronic investigation by DFT calculations confirmed the Ti-N triple bond character implied by the experimentally determined bond length, with the HOMO and HOMO-1 having Ti-N π-bonding character. The dimethylamine ligands of the anion resist substitution by moderate bases but can be displaced by pyridine to give a pentacoordinate anion. In contrast, addition of 2,2'-bipyridyl gives a neutral octahedral complex. Treatment of the pyridine complex with TlCp results in the formation of a four coordinate anionic cyclopentadienyl complex.     

In-house validation study for salmonella unique testing of juice (modification of AOAC official method 2000.07)

Following an industry request, a study was undertaken to validate a minor change to the Unique method for testing fruit juice. Twenty foods were tested in the original precollaborative study for TECRA Unique Salmonella test (2000.07). To validate the modification for juice, both the modified method (42 degrees C module incubation with a 5 h replication step) and the current AOAC Method 2000.07 (37 degrees C incubation with a 4 h replication step) were compared with the U.S. Food and Drug Administration's Bacteriological Analytical Manual (BAM; 8th Ed., 1998) reference method, which uses lactose broth as pre-enrichment medium. Twenty uninoculated replicates, 20 replicates with low-level inoculum (target 1-5 cells/25 g), and 20 replicates with high-level inoculum (target 10-50 cells/25 g) were tested for a single batch of fresh orange juice in accordance with AOAC requirements. There was exact agreement between the 2 Unique methods for all samples and exact agreement between the 2 Unique methods and the BAM method for the uninoculated and high-level inoculum samples. For low-level inoculum, 17 samples were confirmed positive with the new Unique method, 17 with AOAC Method 2000.07, and 14 with the BAM method.     

Microsolvation of the sodium and iodide ions and their ion pair in acetonitrile clusters: a theoretical study

The structural and thermodynamic properties of Na+(CH3CN)n, I-(CH3CN)n, and NaI(CH3CN)n clusters have been investigated by means of room-temperature Monte Carlo simulations with model potentials developed to reproduce the properties of small clusters predicted by quantum chemistry. Ions are found to adopt an interior solvation shell structure, with a first solvation shell containing approximately 6 and approximately 8 acetonitrile molecules for large Na+(CH3CN)n and I-(CH3CN)n clusters, respectively. Structural features of Na+(CH3CN)n are found to be similar to those of Na+(H2O)n clusters, but those of I-(CH3CN)n contrast with those of I-(H2O)n, for which "surface" solvation structures were observed. The potential of mean force calculations demonstrates that the NaI ion pair is thermodynamically stable with respect to ground-state ionic dissociation in acetonitrile clusters. The properties of NaI(CH3CN)n clusters exhibit some similarities with NaI(H2O)n clusters, with the existence of contact ion pair and solvent-separated ion pair structures, but, in contrast to water clusters, both types of ion pairs adopt a well-defined interior ionic solvation shell structure in acetonitrile clusters. Whereas contact ion pair species are thermodynamically favored in small clusters, solvent-separated ion pairs tend to become thermodynamically more stable above a cluster size of approximately 26. Hence, ground-state charge separation appears to occur at larger cluster sizes for acetonitrile clusters than for water clusters. We propose that the lack of a large Na+(CH3CN)n product signal in NaI(CH3CN)n multiphoton ionization experiments could arise from extensive stabilization of the ground ionic state by the solvent and possible inhibition of the photoexcitation mechanism, which may be less pronounced for NaI(H2O)n clusters because of surface solvation structures. Alternatively, increased solvent evaporation resulting from larger excess energies upon photoexcitation or major solvent reorganization on the ionized state could account for the observed solvent-selectivity in NaI cluster multiphoton ionization.     

The use of FTIR and NMR spectroscopies to study prepolymerisation interactions in nitrogen heterocycles

A detailed investigation into the functional groups responsible for the formation of a noncovalent complex between 2-aminopyridine (template) and methacrylic acid (functional monomer) has been carried out using FTIR spectroscopy and confirmed by ¹H NMR spectroscopic data. The approach adopted to confirm the mechanism of interaction was the analysis of the template plus the structurally similar 2-methylaminopyridine and 2-dimethylaminopyridine. A 1:1 stoichiometry of complexation was determined by Job plot analysis following titration, with FTIR results complementing those of the ¹H NMR study. The strength of interaction between 2-aminopyridine and the functional monomer measured through band shifts by FTIR spectroscopy was compared with such interactions for the isomers 3- and 4-aminopyridine. This comparison identified a clear correlation between template pK _a, degree of interaction and subsequent nonspecific binding in the nonimprinted polymer. Using FTIR spectroscopy it was also possible to observe the effect of temperature on the prepolymerisation solution. IR spectra showed that lower temperatures led to more stabilized interactions of the hydrogen-bonded complex. The potential advantages of FTIR spectroscopy compared with ¹H NMR spectroscopy in studying prepolymerisation solutions have been identified.     

A total synthesis of (R,S)S-glucoraphanin

A total synthesis of (R,S)_S-glucoraphanin (GRP) has been completed by a novel, simple and convenient method in high overall yield (17% over seven steps). The study describes a method for the synthesis of natural and unnatural (methylsulfinyl)alkyl glucosinolates (GLs) and also opens useful pathways to synthesize GRP as well as other sulfinyl GLs.     

Novel intramolecular reactivity of oximes: synthesis of cyclic and spiro-fused imines

Under conventional heat (135-145 degrees C) or microwave irradiation and 1 equiv of acetic anhydride, ortho-substituted aryl-oximes undergo a novel sp3 C-H activated cyclization to produce the corresponding isoindoles, and aliphatic oximes afford the corresponding dihydropyrroles. The cyclization occurs with various substrates in good yield (46-82%) leading to unique spiro-fused and cyclic imines. An initial mechanistic investigation suggests the reaction occurs via a nitrenium or vinyl nitrene intermediate. [reaction: see text]     

A Masked Phosphinidene Trapped in a Fluxional NCN Pincer

The trapping of a phosphinidene (R‐P) in an NCN pincer is presented. Stabilized phosphinidene 1 was characterized by ³¹P{¹H}, ¹H, and ¹³C{¹H} NMR spectroscopy, exhibiting an averaged C_2v symmetry in solution between ?60 and 60 °C. In the solid state, the phosphinidene is coordinated by one adjacent N atom featuring a formal P?N bond (1.757(2) Å) to give a five‐membered ring with some aromatic character, confirmed by DFT calculations (B3LYP‐D3/6‐311G**++) to be the ground‐state structure. Equilibration of the two N ligands occurs rapidly in solution via a “bell‐clapper”‐type process through an associative symmetric transition state calculated to lie 4.0 kcal mol^?1 above the ground state.     

From amino acids to heteroaromatics--thiopeptide antibiotics, nature's heterocyclic peptides

Amino acids, the building blocks of proteins, also serve as precursors to a wide range of other naturally occurring substances including alkaloids, antibiotics, and, the subject of this Review, heterocyclic peptides. Simple alpha-amino acids are converted into complex arrays of heteroaromatic rings that display interesting and potent biological activity. The thiopeptide antibiotics, with their complex molecular architectures, are wonderful examples. In this Review we show how organic chemists have developed innovative methods for the synthesis of the heterocyclic ring systems, including routes inspired by the likely biosynthetic processes, and successfully assembled such building blocks into the final target molecule by application of orthogonal protecting groups and coupling methodologies.     

CSF biomarker discovery using label-free nano-LC-MS based proteomic profiling: technical aspects

Biomarker discovery in cerebrospinal fluid (CSF) can provide important information helping to diagnose and monitor disease progression in brain disorders. We present a label-free LC-MS strategy to investigate the proteomic profile of CSF. We provide a framework and protocol addressing quality control, sample replication steps and the adaptation of pattern recognition methods for the detection of experimental variation and (most importantly) putative biomarkers. This strategy was tested using a total of 20 CSF samples (ten samples from healthy volunteers and ten from schizophrenia patients). A clear difference was found between healthy volunteers and schizophrenia patients. With technical and biological variation controlled, we were able to detect 77 proteins with confidence in CSF, of which seven were newly identified, without prior depletion of abundant protein species. Our strategy provides a simple and controlled method for CSF biomarker discovery.     

Total synthesis of bassiatin and its stereoisomers: novel divergent behavior of substrates in Mitsunobu cyclizations

Total syntheses of the morpholine-2,5-dione, Bassiatin, and its stereoisomers have been completed. A key step in the syntheses was the Mitsunobu cyclization of hydroxyacid acyclic precursors. The hydroxyacid precursors are hindered alcohols and two substrates underwent Mitsunobu cyclization with retention of configuration. The other two substrates underwent Mitsunobu cyclization with either retention or inversion of configuration depending on reaction conditions. This divergence in outcome of the Mitsunobu reaction for the same substrate depending on effective concentration is novel.