Code: PI	Time Slot/Poster Number: 136	Session: Liquids Methods: Small Organic Molecules, Poster
Methodological Developments for Discerning of Degenerate Transitions in 1H NMR and Discrimination of Enantiomers
Suryaprakash Nagarajarao
Indian Institute of Science, Bangalore, India
Abstract
Many therapeutic drug molecules generally contain a chiral centre. In the drug molecule containing a single chiral centre one enantiomer may possess the desired pharmaceutical activity while the other enantiomer may be either inactive or exhibit undesirable effect. It is dangerous to administer the inactive enantiomer as the drug. Thus identification, separation and the quantification of enantiomeric excess of one form over the other is of paramount importance in the pharmaceutical industry and also in asymmetric synthesis. An achiral solvent normally employed in solution state NMR does not permit the differentiation of the two enantiomers. Aligning the molecule in a chiral liquid crystalline phase, on the other hand, overcomes this difficulty. Employment of proton detection for such a purpose is severely hampered due to significant loss of resolution arising from the unresolved transitions due to several short and long distance dipolar couplings and the doubling of the spectra from the two enantiomers. In recent times we have developed several novel NMR methodologies to circumvent some of these problems. The remarkable spectral simplification achieved, by discerning the degenerate transitions, enables the determination of spectral parameters from the broad and featureless 1H spectra. The developed methodologies not only aid in unambiguous visualization of enantiomers but also permit the measure of enantiomeric excess. The results of our recent study will be discussed. References 1. Uday Ramesh Prabhu and N. Suryaprakash, J. Magn. Reson. 202, 217-222 (2010) 2.Nilamoni Nath and N. Suryaprakash, J. Magn. Reson. 202, 34-37 (2010) 3.Nilamoni Nath, Bikash Baishya and N. Suryaprakash, J. Magn. Reson. 200, 101-108 (2009) 4.Uday Ramesh Prabhu and N. Suryaprakash, J. Magn. Reson. 195, 145-152 (2008) 5.Uday Ramesh Prabhu, Bikash Baishya and N. Suryaprakash, J. Phys. Chem. A. 112, 5658-5669 (2008) 6.Bikash Baishya, Uday Ramesh Prabhu and N. Suryaprakash, J. Magn. Reson. 192, 101-111 (2008)

Code: PI	Time Slot/Poster Number: 137	Session: Liquids Methods: Small Organic Molecules, Poster
Recent Advances in Non-Empirical Calculations of Spin-Spin Coupling Constants Involving Phosphorous and Selenium Nuclei
Sergey Fedorov; Yury Rusakov; Leonid Krivdin
Irkutsk Institute of Chemistry, Irkutsk, Russian Federation
Abstract
A special interest of this study has been focused on the computational aspects of 31P-1H and 77Se-1H spin-spin coupling constants, which are of major importance in view of the very limited amount of corresponding data obtained at the high level of modern ab initio theory. During this study a very good agreement with experiment was achieved for 31P-1H and 77Se-1H spin-spin coupling constants calculated at the Second Order Polarization Propagator Approach (SOPPA) level in a number of unsaturated organophosphorus and organoselenium compounds. This is especially encouraging in respect with the 77Se-1H couplings showing marked stereochemical behavior and thus providing a versatile tool for the conformational analysis of the related organoselenium compounds. Very interesting conformational trends were also found for the 31P-1H coupling constants in the series of unsaturated phosphines and phosphine chalcogenides.

Code: PI	Time Slot/Poster Number: 138	Session: Liquids Methods: Small Organic Molecules, Poster
Higher-Rank Correlation NMR Spectra with Spectral Moment Filtering
Kerem Bingol1, 2; Roberto Salinas 1, 2; Rafael Bruschweiler1, 2
1Florida State University, Tallahassee, Florida; 2National High Magnetic Field Laboratory, Tallahassee, Florida
Abstract
Long experimental times make high-throughput analysis of synthetic, natural products and complex mixtures by 3D Fourier transform (FT) NMR unaffordable. Here we introduce an alternative approach to 3D FT NMR for the acquisition of multidimensional NMR data named “higher-rank correlation NMR”. Our method combines standard 2D FT spectra that share a common frequency dimension and constructs a higher-rank correlation NMR spectrum with ultrahigh resolution in all frequency dimensions. Spectral overlap along a common dimension is addressed by a spectral filtering method, which identifies mismatches between the first and second moments of cross-peaks, effectively suppressing false peaks. Our method, which provides a substantial speed-up over traditional 3D FT spectroscopy, is demonstrated for the triple-rank 13C-1H HSQC-TOCSY spectrum of a cyclic decapeptide.

Code: PI	Time Slot/Poster Number: 139	Session: Liquids Methods: Small Organic Molecules, Poster
Cross-Correlated Relaxation in a Dipeptide
Judith Schlagnitweit1; Lorenz Reith1; Ladislav Benda2; Jaroslav Sebestík2; Milos Budesinsky2; Vladimír Sychrovsky2; Norbert Muller1
1Johannes Kepler University, Linz, Austria; 2Academy of Sciences of the Czech Republic, Praha, Czech Republic
Abstract
Cross-correlated relaxation, in particular caused by interference between dipole-dipole-interactions and chemical shift anisotropy can provide useful geometry information on large biomolecules. We extended the application of CCR-based methods to smaller molecules where CCR-rates are usually vanishingly small. We used highly viscous mixtures of sorbitol and water as solvents to reduce the rotational correlation times. The inter-conversion of different terms in the density operator by CCR-processes can be measured accurately by symmetrical reconversion pulse sequences. We extended this method by designing pulse programs indirect 1H and direct 13C detection and applied them to 13C- and 15N-labeled alanyl-alanine, dissolved in a highly viscous water-sorbitol mixture. The experimental results were compared to calculated values, obtained by the DFT-method.

Code: PI	Time Slot/Poster Number: 140	Session: Liquids Methods: Small Organic Molecules, Poster
Exploiting Pseudo-Symmetry Relationships in Conformational Analysis using Residual Dipolar Couplings
Armando Navarro-Vázquez1; Raquel Santamaria-Fernandez1; Marcos Battistel2; Victor Sanchez-Pedregal3; Roberto R. Gil2
1Departamento de Quimica Organica. UVigo, Vigo, Spain; 2Department of Chemistry, Carnegie Mellon Universit, Pittsburgh, PA; 3Departamento de Q. Orgánica, USC, Santiago de Compostela, Spain
Abstract
Conformational exchange in small molecules in many cases takes place between enantiomer-like geometries. We propose here a simple approach to exploit these symmetry relationship for the conformational analysis of small molecules by using residual dipolar couplings (RDCs). Conformational equilibria in phenylmenthol and quinine systems are analyzed using this methodology and results compared to other approximations as the single tensor approach.

Code: PI	Time Slot/Poster Number: 141	Session: Liquids Methods: Small Organic Molecules, Poster
Assignment of 19F Chemical Shifts in Monosubstituted Perfluoroparacyclophanes
Ion Ghiviriga; Lianhao Zhang; Henry Martinez ; William Dolbier
Department of Chemistry, University of Florida, Gainesville, FL
Abstract
Perfluororparacyclophanes (PFPCs) display a multitude of 19F-19F couplings, ranging from ca. 250 Hz for the geminal coupling to couplings smaller than 3 Hz. Larger couplings were identified in the DQF-COSY spectrum, confirmed and measured in selective decoupling experiments, and then refined through simulation in gNMR. This work describes a methodology for the assignment of the 19F chemical shifts in PFPCs, based on the 19F-19F couplings.

Code: PI	Time Slot/Poster Number: 142	Session: Liquids Methods: Small Organic Molecules, Poster
NMR Characterization of Synthetic Galactosyl Diglyceride Antigens for Lyme Disease
Bruce Coxon; Vince Pozsgay
National Institutes of Health, Bethesda, MD
Abstract
Detailed NMR assignments have been made for four synthetic 1,2-di-O-acyl-3-O-α-D-galactopyranosyl-sn-glycerols of the BBGL-2 type, and rules developed for the structural dependence of their 13C=O chemical shifts.

Code: PI	Time Slot/Poster Number: 143	Session: Liquids Methods: Small Organic Molecules, Poster
An NMR and Molecular Modelling Study of the Conformational Equilibria In some Novel Heteroaromatic Nitroso Compounds
Ion Ghiviriga1; Bahaa El-Dien M. El-Gendy2; Dmytro Fedoseyenko1; Alan Katritzky1
1University of Florida, Gainesville, FL; 2Department of Chemistry, Benha University, Benha, Egypt
Abstract
Monomer-dimer and conformational equilibria in novel C-nitroso derivatives of indolizines and 3- and 5-azaindolizines have been studied by NMR. Discrimination between monomers and dimers was made on the basis of 13C chemical shifts of the carbon alpha to the nitroso group. The conformers arising from restricted rotation about the C-NO bond in monomers were identified by the chemical shifts of the carbon beta to the nitroso group. Molecular modelling demonstrated that in most cases, the position of the conformational equilibrium is due to steric effects. Ethyl 2-(methylamino)-1-nitrosoindolizine-3- carboxylate displayed conformers arising from the restricted rotation about the C-COOR bond.

Code: PI	Time Slot/Poster Number: 144	Session: Liquids Methods: Small Organic Molecules, Poster
nuup, a web-based implementation of modified J-doubling method in 1- and 2-D NMR experiments for spin-spin coupling measurements
Amed Muñoz-Ramos; Federico del Rio-Portilla
Instituto de Química, UNAM, México, Mexico
Abstract
The modified J-doubling method 1 is a web-based program named nuup (the mayan word for “coupling” and hosted on http://labna.iquimica.unam.mx/nuup/). As a web program, the calculation of coupling constants from 1- and 2-D NMR spectra is made graphically regardless of the operating system or web browser of the user. After the deconvolution process involved in the calculation of each value of J in one single multiplet, a new multiplet simplified in multiplicity is obtained, ready for a new calculation. Through some steps, the user is allowed to modify J-doubling parameters and perform the calculation of J. This implementation of the method is specially useful for mutiplets with several coupling constants.

Code: PI	Time Slot/Poster Number: 145	Session: Liquids Methods: Small Organic Molecules, Poster
An Enhanced Method For Determining Enantiomeric Excess by 13C-NMR in Chiral Liquid Crystal Media
Vasilios Marathias1, 1; Peter Tate1, 2; Nikolaos Papaioannou1, 2; Walter Massefski1, 2
1, Cambridge, MA; 2Pfizer Inflammation / Immunology Research Unit, Cambridge, MA
Abstract
By using a combination of inverse gated 1H decoupled 13C-NMR experiments with short acquisition times and NMR Cryo-probe technology, the sample requirements and experimental times necessary to accurately measure enantiomeric excess of small chiral molecules has been reduced 16 fold.

Code: PI	Time Slot/Poster Number: 146	Session: Liquids Methods: Small Organic Molecules, Poster
Probing Dynamic Coupling in Cryptophane Inclusion Complexes with Liquid Crystal NMR and Quantum Chemical Calculations
Peter Nikolaou1; Alisha Lemons5; Kathleen Chaffee2; Breina Burgin4; Jean-Pierre Dutasta3; Thierry Brotin3; Boyd M. Goodson1
1Southern Illinois University, Carbondale, IL; 2Washington University, St. Louis, MO; 3École Normale Supérieure de Lyon, Lyon, France; 4Upper Iowa University, Fayette, IA; 5Northwest Missouri State University, Maryville, MO
Abstract
We report on our ongoing efforts to study host-guest dynamic coupling in cryptophane inclusion complexes aligned in liquid crystal (LC) matrices. The effects of systematically varying the host and guest properties on the resulting host-guest behavior are studied via CP-enhanced 13C VTNMR. Dipolar couplings measured from guest NMR depend sensitively upon the host cavity volume, as manifested by differential alignments of bound guests that are directly proportional to the host-guest occupancy factor. In order to gain greater understanding of such observations, we have begun computational (DFT) studies of cryptophane complex structures and energetics. These efforts should ultimately allow predictions of energy barriers for internal rotations of guests (and host-guest exchange) to be compared with our LCNMR results.

Code: PI	Time Slot/Poster Number: 147	Session: Liquids Methods: Small Organic Molecules, Poster
Variable-Temperature NMR Studies of Complexation of Molecular Hydrogen (H2) by Cryptophane-111: Evidence for Multiple H2 Binding under Mild Conditions
Kathleen Chaffee1, 3; Ping He1; Heather Fogarty2; Jean-Pierre Dutasta2; Boyd Goodson1; Thierry Brotin2
1SIUC, department of Chemistry, Carbondale, IL; 2École Normale Supérieure de Lyon, Lyon, France; 3Washington University St. Louis, St. Louis, MO
Abstract
We report ongoing studies of the binding of molecular hydrogen (H2) by cryptophane-111 (C111) in solution by variable-temperature 1H NMR. Fast exchange is observed throughout the entire temperature range yet studied, even at 800 MHz. When the C111 concentration is relatively high, the single 1H H2 resonance is observed to shift strongly upfield with decreasing temperature; however, at lower concentrations the behavior is more complex—including a notable change in the direction of the shift at ~230 K. Indeed, the observed 1H NMR behavior deviates significantly from what would be expected for transient formation of 1:1 complexes. We are developing a model that indicates that the observed behavior is at least qualitatively consistent with multi-guest binding by the host.

Code: PI	Time Slot/Poster Number: 148	Session: Liquids Methods: Small Organic Molecules, Poster
Doubly selective excitation method (Exclusive SHEHAHA) implementation for “isotagged” oligosacharide structure elucidation
Clark Ridge2; Federico Del Rio-Portilla1; Yuanchang Sun2; Jack Xin2; A. J. Shaka2
1Instituto de Química, UNAM, Mexico D. F. , México; 2University of California at Irvine, Irvine, California
Abstract
“Exclusive HEHAHA” 1D sequence is proposed for “isotagged” oligosacharide solution structure elucidation. Double selective heteronuclear Hartman-Hahn transfer experiment is proposed for individual in-phase selective proton spectra between the “isotagged” 13CO and the proximal proton on the sugar ring. An excitation sculpting double pulsed field gradient spin echo was used to improve selection of a particular carbonyl carbon resonance. Several pulsed field gradients are used to clean the multiplet, avoiding zero and multiple quantum coherences produced due to the long “soft” heteronuclear Hartman-Hahn transfer. Multiplet extractions are clean enough to determine proton-proton coupling constants which are extremely important for identification of sugar type.

Code: PI	Time Slot/Poster Number: 149	Session: Liquids Methods: Small Organic Molecules, Poster
Selective J-resolved -HMQC, A New Method for Measuring Proton-Proton Coupling Constants of High Order Spin System.
Kazuo Furihata
University of Tokyo, Tokyo, Japan
Abstract
Overlapping protons or strongly coupled protons make analysis of H-H J coupling constant difficult. This problem can be solved by utilizing a proton attached to 13C. In order to overcome this problem, we developed a new method, selective J-resolved HMQC by decoupling two adjacent protons. In this method, only two strongly coupled protons, HA and HB being excited by selective pulse are observed as J-resolved HMQC signals. As a result, the cross peaks of HA and HB appeared as doublets with adjacent protons being decoupled in f1 dimension. Application of this method to a model compound, monazomycin with a complicated structure proved its effectiveness for stereochemical studies.

Code: PI	Time Slot/Poster Number: 150	Session: Liquids Methods: Small Organic Molecules, Poster
Adiabatic 13C NMR Pulse Sequences for high precision Quantitative Measurement
Christophe Thibaudeau; Gérald Remaud; Virginie Silvestre; Serge Akoka
CEISAM, UMR 6230, CNRS/Université de Nantes, Nantes, France
Abstract
The single-pulse 13C-NMR sequence was successfully used for precise, accurate and reproducible 13C-NMR measurements. However, measuring times of several hours associated with this sequence constitute a serious drawback. In this work, several NMR pulse sequences were optimised to measure precise quantitative 13C-NMR spectra within a short time. Adiabatic 180° 1H and 13C pulses were incorporated into DEPT and INEPT. A modified HCP experiment featuring 1H and 13C adiabatic spin-locks is also introduced. Our results clearly show that the use of adiabatic 1H and 13C 180° pulses significantly improves the repeatability of the measurements. The adiabatic DEPT and INEPT sequences both have the potential to be used in high precision quantitative 13C NMR.