Hadamard NMR spectroscopy in solids

The duration of 2D and 3D NMR experiments in solids can be reduced by several orders of magnitude by using frequency domain Hadamard encoding with long selective pulses. We demonstrate Hadamard encoded experiments in (13)C enriched solids samples. To avoid multiple quantum interferences, the Hadamard encoding pulses are applied sequentially rather than simultaneously in this study. Among other possible applications, dipolar assisted rotational resonance experiments and measurement of NOESY type build-up rates in proton driven spin diffusion are demonstrated.     

Binding of calcium to amino acids (2)

Crystal structures ofN-acetyl-(DL)-methionine and its calcium adduct have been determined in order to examine possible calcium coordination through sulfur atom and conformation changes in the molecule upon calcium coordination. Crystals of the Ca adduct ofN-acetyl-(DL)-methionine are triclinic, space groupP¯1, a=11.356(2) Å,b=13.556(2) Å,c=15.035(3) Å,=95.42(1)°,=103.66(1)°, and=103.66(1)°, withZ=4 andd _o= 1.40 g cm^–3; 5834 reflections were collected at –125°C. TheN-acetyl-(DL)-methionine was also crystallized so that changes induced by the calcium coordination could be observed. TheN-acetyl-(DL)-methionine crystals are monoclinic, space groupP2₁/c,a=5.885(1) Å,b=9.290(1) Å,c=18.024(2) Å,=92.51 (1)°, withZ=4 andd _o=1.30 g cm^–3. Both structures were solved using direct methods and refined using full matrix least squares. The final values ofR andR _w were 0.051 and 0.053 for the Ca adduct and 0.048 and 0.039 for the free amino acid. All hydrogen atoms were located and included in the final calculations. Interatomic distances and angles of the four crystallographically independentN-acetylmethionine molecules in the Ca adduct are comparable to those of the free molecule, but the torsion angles change drastically. Calcium coordination through the sulfur atom is not found. The binding modes of all four independentN-acetylmethionine molecules in the Ca adduct are different. Of the two crystallographically independent calcium atoms one is 6 and the other is 7 coordinated. The calcium adduct shows several Ca-Ca bridges (with distances 4.722, 4.746, 5.503, and 6.265 Å) which can be described as a zigzag calcium chain or alternatively as slightly puckered sheets of calcium atoms parallel to theab plane atz O.     

Monomers for preparation of amide-linked RNA: asymmetric synthesis of all four nucleoside 5'-azido 3'-carboxylic acids

[reaction: see text] Recent discovery of RNA interference as an efficient and naturally occurring mechanism of gene regulation has reinvigorated the interest in chemically modified RNA. For potential in-vivo applications small interfering RNAs require chemical modifications to fine-tune the thermal stability and increase the cellular delivery and potency and in vivo half-life of the RNA duplexes. From this perspective, amides as neutral and hydrophobic internucleoside linkages in RNA are highly interesting modifications for RNA interference. Amides are remarkably good mimics of the phosphodiester backbone of RNA and can be prepared using a relatively straightforward peptide coupling chemistry. However, the progress in the field has been hampered by the shortage of efficient methods to synthesize the monomeric building blocks for such couplings, the nucleoside amino acid equivalents. Herein, we report enantioselective synthesis of 5'-azido 3'-carboxylic acid derivatives of all four natural ribonucleosides. The key transformations in our synthesis are a double asymmetric ene reaction and a stereoselective iodolactonization that form the basic carbon skeleton of the modified ribose. Standard nucleoside synthesis is followed by a short and highly efficient protecting group manipulation to give the enantiomerically pure (>98%) title compounds in 9-10 steps and 15-19% overall yields starting from small achiral molecules. The present results are a significant improvement over our first-generation racemic synthesis and compare favorably with the previously reported synthesis from nucleoside and carbohydrate precursors.     

Parallel acquisition of two-dimensional NMR spectra of several nuclear species

We show that two or more two-dimensional NMR correlation spectra can be recorded in a single shot, using a multicoil radio-frequency probe and receiver system designed for simultaneous parallel acquisition of signals from different nuclear species such as 1H, 13C, and 15N. Dubbed PANSY (parallel acquisition NMR spectroscopy), this new technique shows promise for recording several multidimensional NMR spectra of different nuclear species in a very short time.