“CLASSIC NMR”: An In‐Situ NMR Strategy for Mapping the Time‐Evolution of Crystallization Processes by Combined Liquid‐State and Solid‐State Measurements

A new in‐situ NMR strategy (termed CLASSIC NMR) for mapping the evolution of crystallization processes is reported, involving simultaneous measurement of both liquid‐state and solid‐state NMR spectra as a function of time. This combined strategy allows complementary information to be obtained on the evolution of both the solid and liquid phases during the crystallization process. In particular, as crystallization proceeds (monitored by solid‐state NMR), the solution state becomes more dilute, leading to changes in solution‐state speciation and the modes of molecular aggregation in solution, which are monitored by liquid‐state NMR. The CLASSIC NMR experiment is applied here to yield new insights into the crystallization of m‐aminobenzoic acid.     

Synthesis,Structure, and Reactivity of a Gold Carbenoid Complex That Lacks Heteroatom Stabilization

Hydride abstraction from the neutral gold cycloheptatrienyl complex [( P )Au(η¹‐C₇H₇)] ( P =P(tBu)₂(o‐biphenyl)) with triphenylcarbenium tetrafluoroborate at ?80 °C led to the isolation of the cationic gold cycloheptatrienylidene complex [( P )Au(η¹‐C₇H₆)]⁺ BF₄^? in 52 % yield, which was characterized in solution and by single‐crystal X‐ray diffraction. This cycloheptatrienylidene complex represents the first example of a gold carbenoid complex that lacks conjugated heteroatom stabilization of the electron‐deficient C1 carbon atom. The cycloheptatrienylidene ligand of this complex is reactive; it can be reduced by mild hydride donors, and converted to tropone in the presence of pyridine N‐oxide.     

Comparative study of free energies of solvation of phenylimidazole inhibitors of cytochrome P450cam by free energy simulation,AMSOL, and Poisson Boltzmann methods

Free energies of solvation of phenylimidazole inhibitors of cytochrome P450cam were determined using (1) free energy simulation, (2) AMSOL-SM2 semiempirical methods, and (3) Poisson-Boltzmann methods. The goals of this study were threefold: (1) to compare the results obtained from the three different methods, (2) to investigate the effect of inclusion of intraperturbed group interactions on free energy simulation estimates of solvation free energy differences, and (3) to investigate to what extent differences in free energies of solvation among three of these inhibitors could account for observed differences in their enzyme binding free energies. In general, relative solvation free energies obtained from the free energy simulations and AMSOL-SM2 methods give comparable results (i.e., the same rank ordering and similar quantitative results, differing significantly from results obtained using Poisson-Boltzmann methods). The free energy simulation studies suggest that the neglect of intraperturbed group interactions had little effect on rank order of free energies of solvation of the polar phenylimidazoles. The relative desolvation free energies of the three inhibitors of P450cam—1-phenylimidazole (1-PI), 2-phenylimidazole (2-PI), and 4-phenylimidazole (4-PI)—with known enzyme bound X-ray structures parallel that of their known binding affinities and could account for most of the differences in the free energies of binding of these three inhibitors to P450cam. The origin of the difference of the free energies of solution of these three inhibitors is primarily the additional interaction between solvent and N(SINGLE BOND)H group in the imidazole ring of 2- and 4-phenylimidazole that is absent in the 1-phenylimidazole isomer. This hypothesis is substantiated by a second comparison of the relative solvation free energies of 4-phenylimidazole with its methylated derivative, 3-methyl-4-phenylimidazole, also lacking an N(SINGLE BOND)H group. © 1996 by John Wiley & Sons, Inc.     

Synthesis of Novel C/D Ring Modified Bile Acids

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.     

Regioselective silylation of sugars through palladium nanoparticle-catalyzed silane alcoholysis

Palladium(0)-catalyzed silane alcoholysis was applied to sugars for the first time using tert-butyldimethylsilane (TBDMS-H) and Ph(3)SiH as the silanes. The catalyst is a colloidal solution of Pd(0) generated in situ from PdX(2) (X = Cl(-), OAc(-)) and TBDMS-H in N,N-dimethylacetamide. The colloid has been characterized by dynamic light scattering and transmission electron microscopy and consists of catalytically highly active nanoparticles of approximately 2 nm diameter. The silane alcoholysis reaction is an effective method for the regioselective silylation of methyl and phenyl glycosides and generates hydrogen gas as the only side product. For many of the sugar substrates investigated, the distribution of regioisomers obtained is complementary to that of the traditional R(3)SiCl/base (base = pyridine, imidazole) methodology and gives convenient access to the 3,6- rather than the 2,6-silylated pyranosides, obtained as the main product by the silyl chloride method. The method also allows a selective axial silylation of levoglucosan and 1,3,5-O-methylidene-myo-inositol. In an attempt to rationalize the observed regioselectivities, ab initio predictions (HF/3-21G) have been made on the relative energies of some of the silylated products. They suggest that the observed regioselectivities do not reflect a kinetic vs thermodynamic product distribution but are induced by the silylation agent employed. Models for the possible origin of the observed regioselectivity in both silylation methods (silane- and silyl chloride-based) are discussed.     

Measurements of the cross section for e(+)e(-) --> hadrons at center-of-mass energies from 2 to 5 GeV

We report values of R = sigma(e(+)e(-)-->hadrons)/sigma(e(+)e(-)-->mu(+)mu(-)) for 85 center-of-mass energies between 2 and 5 GeV measured with the upgraded Beijing Spectrometer at the Beijing Electron-Positron Collider.     

Routine preparation of air-dried negatively stained and unstained specimens on holey carbon support films: a review of applications

Several representative examples are given of the successful application of negative staining across the holes of holey carbon support films using 5% (w/v) ammonium molybdate solution containing trehalose. The inclusion of 0.1% (w/v) trehalose is considered to be most satisfactory, although good data have also been obtained in the presence of 0.01 and 1.0% (w/v) trehalose. The examples given fall into the following groups: protein molecules in the absence of polyethylene glycol (PEG), protein molecules in the presence of PEG (Mr 1000), lipoproteins, lipids and membranes, filaments and tubules, viruses in the absence of PEG, viruses in the presence of PEG, aqueous polymer solutions, and finally for comparison purposes, four unstained samples studied in the presence of trehalose alone. In all these cases, and many others not documented here, successful spreading of the sample across holes has been achieved, with the sample embedded within a thin film of air-dried ammonium molybdate+trehalose. These specimens can be rapidly produced and provide an alternative to negatively stained specimens on carbon support films. Specimen stability in the electron bean is good and such specimens can usually generate superior negatively stained TEM images without flattening and adsorption artefacts. The formation of 2-D arrays/crystals of protein molecules and viruses, suspended across holes in the presence of ammonium molbybdate+trehalose, and trehalose alone, is also demonstrated.     

6Li and 7li solid-state NMR spectroscopy of nitrogen ceramic phases

Two nitrogen ceramic phases, the oxynitride LiSiON and the nitride LiSi2N3, have been studied by 6Li and 7Li NMR. Magic angle spinning (MAS) NMR experiments have been carried out at two magnetic field strengths (7.05 and 14.1 T). The spectra give evidence of the relative effects of the quadrupolar and chemical shift interactions. The electric field gradient tensor of both phases has been determined accurately by iterative fitting of the 6Li and 7Li MAS NMR line shapes at the two magnetic field strengths. Due to the fact that for 7Li the quadrupolar interaction is much larger than the chemical shift interaction, it is shown that neither the small chemical shift anisotropy nor the relative orientation of the two interaction tensors can be determined accurately by 7Li MAS NMR. For 6Li, the two interactions are comparable and the value of these parameters obtained from the fits of the 6Li experimental MAS line shapes are therefore much more reliable.