Code: PT	Time Slot/Poster Number: 403	Session: Solids: Small Molecules, Poster
Conformational dynamics of methyl group of crystalline L-methionine
Kuo-Ying Huang; Ann McDermott
Columbia University, New York, NY
Abstract
Crystalline L-methionine is well known for its sidechain dynamics. There are two conformers in crystal structure: the all trans form (referring to the Cε–S–Cγ–Cβ and S–Cγ–Cβ–Cα torsions) and the gauche-gauche form. These two conformers exchange slowly (on the timescale of hundreds of ms), and give rise to two resolvable 13C chemical shifts on methyl sites. The methyl rotations of these two conformers on L-methionine have lower order parameters compared to the methyl rotations of L-alanine, DL-valine, DL-Thionine, or L-Leucine when the temperature is higher than 20oC. The methyl group order parameters of each conformer of L-methionine can be obtained by measuring deuterium quadrupolar tensors via 2H-13C Cross Polarization experiments.

Code: PT	Time Slot/Poster Number: 404	Session: Solids: Small Molecules, Poster
Spectral Editing Methods Employing Homonuclear 1H Decoupling:Towards Better Characterisation of Pharmaceutical Solids
Andrew S. Tatton1; Tran N. Pham2; Steven P. Brown1
1University of Warwick, Coventry, UK; 2GlaxoSmithKline, Stevenage, UK
Abstract
In CPMAS solid-state NMR of moderately sized organic solids, such as those used as active pharmaceutical ingredients, it is important to be able to assign the distinct observed resonances according to their proton multiplicity (i.e., CH3, CH2, CH or quaternary). A heteronuclear spin-echo spectral editing sequence incorporating 1H homonuclear decoupling allows magnetisation to evolve under J couplings only; therefore zero crossings only occur for odd multiplicities. Multi-spin density-matrix simulations are used to understand the factors affecting optimum homonuclear 1H decoupling performance as observed experimentally on model compounds. Specifically, the dependence on rf nutation frequency as well as the role of homonuclear and heteronuclear dipolar couplings is considered.

Code: PT	Time Slot/Poster Number: 405	Session: Solids: Small Molecules, Poster
Selective F-19 to C-13 Cross Polarization, a Novel Tool for Structure Elucidation in Pharmaceuticals
George B. Crull; John Grosso; Raymond Scaringe
Bristol-Myers Squibb, New Brunswick, NJ
Abstract
The importance of ssNMR for pharmaceutical solids is well established. Capable of providing information comparable to combined single crystal and powder diffraction techniques, ssNMR, provides additional complementary information and is typically more sensitive to the presence of amorphous phases. We now routinely exploit fluorine as a stable label probe to assign carbon spectra. We utilize two distinct F-19 to C-13 CPMAS experiments: 1) a conventional F-19 to C-13 CPMAS; 2) a pulse sequence using a selective fluorine excitation pulse. Varying the contact time, carbons more spatially remote to the fluorine can be identified in a sequential manner. Applying a selective fluorine excitation pulse, carbons near the specific fluorine can be assigned in molecules or crystals with multiple resolved fluorine resonances.

Code: PT	Time Slot/Poster Number: 406	Session: Solids: Small Molecules, Poster
Preliminary studies of the dynamics of an elastin mimetic peptide, (VPG*VG*)3 by deuterium NMR spectroscopy
Xiang Ma; Gregory Boutis
Brooklyn College of The City University of New Yor, Brooklyn , NY
Abstract
The polypentapeptide (VPGVG)n serves as a useful model for characterizing structure and dynamics of elastin, a major protein constitute of connective tissues. In this poster we report on a preliminary experimental study of a deuterated (VPG*VG*)3 peptide by deuteron NMR spectroscopy. For a powdered sample at room temperature, we have successfully measured the quadrupolar echo spectra. Using available simulation tools, we obtained the quadrupolar coupling coefficient δ ≈120kHz as well as other parameters in the two-site rotational model. Experiments of this and other deuterated peptides are ongoing and will be used for providing an understanding of the dynamics occurring in this system.

Code: PT	Time Slot/Poster Number: 407	Session: Solids: Small Molecules, Poster
Vibrational self-consistent field calculations and 2H solid-state NMR of the Zundel cation
Jun Zhou; Gerard Harbison
University of Nebraska-Lincoln, Lincoln, NE
Abstract
The Zundel cation, (H2O...H+...OH2), forms a series of crystalline salts with strong acids at low temperatures. 2H NMR of the deuterated cation shows distinct signals from the strongly hydrogen bonded central and weakly hydrogen bonded peripheral deuterons. At deuteration levels less than 100%, deuterons partition out of the central position. This thermodynamic isotope effect was modeled successfully using vibrational self consistent field (VSCF) quantum chemical methods that fully account for the anharmonicity of the bonds, particularly the strong hydrogen bond. VSCF also allows us to accurate calculate the deuteron CQ, and shows this to be an unusual example of a true single-well strong hydrogen bond.

Code: PT	Time Slot/Poster Number: 408	Session: Solids: Small Molecules, Poster
Improved referencing for 31P experimental and computed chemical shifts
Adrienne M. Roehrich; Gerard S. Harbison
University of Nebraska, Lincoln, NE
Abstract
Phosphorus-31 NMR uses 85% H3PO4 as a reference, which is suitable for liquid and even solid-state experimental NMR, but is computationally intractable. 31P NMR computations of chemical shifts therefore typically require a two-stage referencing process. A crystalline reference compound, if experimentally and computationally convenient, would make these corrections more direct. We propose ammonium dihydrogen phosphate (ADHP), whose isotopic chemical shift is very close to 85% H3PO4. ADHP has a chemical shielding anisotropy and dipolar interactions small enough to be observed even with very modest r.f. power, and its crystal structure is highly symmetric. ADHP can therefore be adequately modeled using a S4-symmetric cluster, an Abelian point group which is highly computationally tractable.

Code: PT	Time Slot/Poster Number: 409	Session: Solids: Small Molecules, Poster
Detection of slow conformational movement: Dipolar CODEX
Wenbo Li; Ann McDermott
Columbia University, New York, NY
Abstract
A solid state NMR experiment is described for probing relatively slow conformational exchange processes, based on a previously described CODEX experiment. In this application, the dipolar coupling is recoupled before and after a long mixing time during which molecular reorientation occurs. The advantage of this method is that the dipolar coupling values are known a priori from molecular structures, and their orientations and reorientations relate in a simple way to molecular geometry and motion. The experiment on 13C, 15N enriched crystalline urea shows that the motion of the chemical bond between isotopic labeled atoms is determined unambiguously. Combined with an appropriate selective isotropic enrichment scheme, this experiment has the potential to detect dynamics in unique sites of complex biopolymers.

Code: PT	Time Slot/Poster Number: 410	Session: Solids: Small Molecules, Poster
A 1H Solid-State NMR Investigation of Polymorphism in Indomethacin.
Jonathan Bradley1; Sitaram Velaga2; Oleg Antzutkin1, 2; Steven Brown1
1University of Warwick, Coventry, United Kingdom; 2Luleå University of Technology, Luleå, Sweden
Abstract
Structural information regarding proton proximities in solids is provided by 1H double-quantum (DQ) spectroscopy. We have recently shown that quantitative information about H-H proximities can be obtained from the build-up of DQ peak intensity in 1H DQ CRAMPS spectra recorded with increasing numbers of POST-C7 recoupling elements. These build-up curves allow the reliable determination of relative H-H distances. Solid-state NMR spectra have been recorded for two polymorphs of the pharmaceutical molecule, indomethacin; and for a indomethacin-saccharin co-crystal. Double-quantum build-up curves have been obtained from 1H DQ CRAMPS spectra, with the 1H chemical shifts assignment based on 1H-13C MAS-J-INEPT correlation spectra and first-principles GIPAW calculations of the chemical shifts using the known crystal structures.