Determination of sugar structures in solution from residual dipolar coupling constants: methodology and application to methyl beta-D-xylopyranoside

We have developed methodology for the determination of solution structures of small molecules from residual dipolar coupling constants measured in dilute liquid crystals. The power of the new technique is demonstrated by the determination of the structure of methyl beta-d-xylopyranoside (I) in solution. An oriented sample of I was prepared using a mixture of C(12)E(5) and hexanol in D(2)O. Thirty residual dipolar coupling constants, ranging from -6.44 to 4.99 Hz, were measured using intensity-based J-modulated NMR techniques. These include 15 D(HH), 4 (1)D(CH), and 11 (n)D(CH) coupling constants. The accuracy of the dipolar coupling constants is estimated to be < +/- 0.02 Hz. New constant-time HMBC NMR experiments were developed for the measurement of (n)D(CH) coupling constants, the use of which was crucial for the successful structure determination of I, as they allowed us to increase the number of fitted parameters. The structure of I was refined using a model in which the directly bonded interatom distances were fixed at their ab initio values, while 16 geometrical and 5 order parameters were optimized. These included 2 CCC and 6 CCH angles, and 2 CCCC and 6 CCCH dihedral angles. Vibrationally averaged dipolar coupling constants were used during the refinement. The refined solution structure of I is very similar to that obtained by ab initio calculations, with 11 bond and dihedral angles differing by 0.8 degrees or less and the remaining 5 parameters differing by up to 3.3 degrees . Comparison with the neutron diffraction structure showed larger differences attributable to crystal packing effects. Reducing the degree of order by using dilute liquid crystalline media in combination with precise measurement of small residual dipolar coupling constants, as shown here, is a way of overcoming the limitation of strongly orienting liquid crystals associated with the complexity of (1)H NMR spectra for molecules with more than 12 protons.     

Effects of thioamide substitutions on the conformation and stability of alpha- and 3(10)-helices

Thiopeptides, formed by replacing the amide oxygen atom with a sp(2) sulfur atom, are useful in protein engineering and drug design because they confer resistance to enzymatic degradation and are predicted to be more rigid. This report describes our free molecular dynamics simulations with explicit water and free energy calculations on the effects of thio substitutions on the conformation of alpha-helices, 3(10)-helices, and their relative stability. The most prominent structural effect of thio substitution is the increase in the hydrogen bond distance from 2.1 A for normal peptides to 2.7 A for thiopeptides. To accommodate for the longer C[double bond]S...H-N hydrogen bond, the (phi, psi) dihedral angles of the alpha-helix changed from (-66 degrees, -42 degrees) to (-68 degrees, -38 degrees), and the rise per turn increased from 5.5 to 6.3 A. For 3(10)-helices, the (phi, psi) dihedral angles (-60 degrees, -20 degrees) and rise per turn (6.0 A) changed to (-66 degrees, -12 degrees) and 6.8 A, respectively. In terms of relative stability, the most prominent change upon thio substitution is the decrease in the free energy difference, Delta A(alpha --> 3(10)), from 14 to 3.5 kcal/mol. Therefore, normal peptides are less likely to form 3(10)-helix than are thiopeptides. Component analysis of the Delta A(alpha --> 3(10)) reviews that the entropy advantage of the 3(10)-helix for both Ac-Ala(10)-NHMe and Act-Alat(10)-NHMe is attributed to the 3(10)-helix being more flexible than the alpha-helix. Interestingly, upon thio substitution, this differential flexibility is even more apparent because the alpha-helix conformation of Act-Alat(10)-NHMe becomes more rigid due to the bulkier sulfur atom.     

Wild ginseng grows in Myanmar

Ginseng, the underground parts of plants of Panax species, has been used in oriental traditional medicine for centuries. Unfortunately, because of extensive exploitation over thousands of years, the natural source of these species has been almost exhausted. Recently, we have found a wild ginseng growing in Myanmar. Here, by a combination of chemical composition study and gene sequence analysis, we unambiguously demonstrate that the wild ginseng is actually P. zingiberensis, commonly known as ginger ginseng. This ginseng was an indigenous to the southwestern China. However, now it is seriously threatened to brink of extinction and is put on the highest level of protection in China. Therefore, an appropriate protection measure is highly recommended to preserve this valuable resource, since this Myanmar ginseng might turn out to be the last P. zingiberensis, which could ever be seen in the planet.     

Link between the kinetic‐ and exchange‐energy functionals in the generalized gradient approximation

An approximate kinetic‐energy functional of the generalized gradient approximation form was derived following the “conjointness conjecture” of Lee, Lee, and Parr. The functional shares the analytical form of its gradient dependency with the exchange‐energy functionals of Becke and Perdew, Burke, and Ernzerhof. The two free parameters of this functional were determined using the exact values of the kinetic energy of He and Xe atoms. A set of 12 closed‐shell atoms was used to test the accuracy of the proposed functional and more than 30 others taken from the literature. It is shown that the conjointness conjecture leads to a very good class of kinetic‐energy functionals. Moreover, the functional developed in this work is shown to be one of the most accurate despite its simple analytical form. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002     

An application of the phosphine-catalyzed [4 + 2] annulation in indole alkaloid synthesis: formal syntheses of (+/-)-alstonerine and (+/-)-macroline

[reaction: see text] An application of the phosphine-catalyzed [4 + 2] annulation in the formal synthesis of alstonerine and macroline is reported. A phosphine-catalyzed [4 + 2] reaction between imine 7a and allene 8 formed the D ring of the target indole alkaloids. A subsequent intramolecular Friedel-Crafts acylation provided the C ring of the bridged tetracycle. Deprotection, followed by methylation of the bridged nitrogen, deoxygenation of the C6 ketone, and reduction of the C16 carbethoxy group provided the previously known intermediate 3.     

Femtosecond time resolved coherent anti-Stokes Raman spectroscopy: experiment and modelization of speed memory effects on H2-N2 mixtures in the collision regime

With the aim of temperature diagnostic, femtosecond time-resolved CARS (coherent anti-Stokes Raman spectroscopy) is applied to probe H2 in H2-N2 mixtures. In a first part, a Lorentzian profile is used to model the femtosecond CARS response. A difference between the experimental broadening and the expected one is observed in the collision regime. The observed broadening increases strongly in an inhomogeneous way with respect to the perturber concentration. This is of considerable importance for temperature measurements. In a second part, we show that in the collision regime, this inhomogeneous broadening is due to the speed dependence of the collisional parameters and the memory effects of the radiator speed. A new modelization of the time-resolved CARS response taking into account the speed memory effects is presented and applied to the temperature diagnostic in H2-N2 mixtures. The numerical results are in good agreement with experiments.     

High-pressure adsorption capacity and structure of CO2 in carbon slit pores: theory and simulation

We present new simulation results for the packing of single-center and three-center models of carbon dioxide at high pressure in carbon slit pores. The former shows a series of packing transitions that are well described by our density functional theory model developed earlier. In contrast, these transitions are absent for the three-center model. Analysis of the simulation results shows that alternations of flat-lying molecules and rotated molecules can occur as the pore width is increased. The presence or absence of quadrupoles has negligible effect on these high-density structures.     

Crystal Structures of Twisted Di(2-Pyridyl)ketone and Planar Azo-di(2-Pyridine) and Their Discussion Based on PM3 Enthalpy Hypersurfaces for the Isoelectronic Molecules

Single crystal structure determinations prove the two pyridine substituents in di(2-pyridyl)ketone (H₄C₄NC)₂C=O to be twisted out of the carbonyl skeleton plane by torsion angles (OCCN) of 41° and –163°, in contrast to their planar arrangement in azo-di(2-pyridine) H₄C₄NC)-N=N-(CNC₄H₄). In order to rationalize the surprising difference between the two isoelectronic molecules, approximate PM3 enthalpy of formation hypersurfaces have been calculated for each of the two ring torsions, which are assumed to be the dominant ones among the 3N – 6 = 60 degrees of freedom. For both the ketone and the azo derivative, global minima are calculated, the torsion angles of which deviate from the crystal structure results, and, therefore, support the assumption that both the experimentally determined twisting of di(2-pyridyl)ketone as well as the flattening of azo-di(2-pyridine) might be affected by the crystal packing.     

Synthesis and spectral characterization of some complexes of platinum(II) containing η-methyleugenol

Several complexes of the formula trans-[Pt(Meug)(Am)Cl₂], Meug: methyleugenol (4-allyl-1,2-dimethoxybenzene), a η²-coordinated olefin, and Am: ammine, methylamine, diethylamine, o-toluidine, m-toluidine, p-toluidine, o-anisidine, m-anisidine and p-anisidine have been prepared. UV, IR, Raman, ¹H NMR, ¹³C NMR and 2D NMR spectra of the complexes were recorded and analyzed.