Magnetic Resonance in Chemistry

Sakellariou, Dimitris; Hugon, Cédric; Guiga, Angelo; Aubert, Guy; Cazaux, Sandrine; Hardy, Philippe

doi: 10.1002/mrc.2683pmid: 20891027

We introduce a cylindrical permanent magnet design that generates a homogeneous and strong magnetic field having an arbitrary inclination with respect to the axis of the cylinder. The analytical theory of 3 D magnetostatics has been applied to this problem, and a hybrid magnet structure has been designed. This structure contains two magnets producing a longitudinal and transverse component for the magnetic field, whose amplitudes and homogeneities can be fully controlled by design. A simple prototype has been constructed using inexpensive small cube magnets, and its magnetic field has been mapped using Hall and NMR probe sensors. This magnet can, in principle, be used for magic angle field spinning NMR and MRI experiments allowing for metabolic chemical shift profiling in small living animals. Copyright © 2010 John Wiley & Sons, Ltd.

Hu, Jun; Eriksson, Per‐Olof; Kern, Gunther

doi: 10.1002/mrc.2692pmid: 21038321

One‐dimensional NMR spectroscopy has proven to be a powerful technique for screening compound libraries in drug discovery. We report a novel water ligand‐observed gradient spectroscopy (WaterLOGSY) pulse sequence, named Aroma WaterLOGSY, that selectively detects aromatic WaterLOGSY signals from compounds or ligands. In the Aroma WaterLOGSY, water magnetization is untouched after water excitation and utilizes the whole period of the remaining pulse sequence to relax back to the + z direction. Due to the phase cycling design, the water magnetization is allowed to relax for the period of two full scans before it gets inverted again. Therefore, the recycle delay can be significantly shortened. Within similar experimental time, Aroma WaterLOGSY shows approximately two times higher sensitivity than the standard scheme. This method also allows the use of non‐deuterated reagents, thereby accelerating experimental set‐up time for ligand‐binding studies. Copyright © 2010 John Wiley & Sons, Ltd.

George, Christy; Chandrakumar, Narayanan

doi: 10.1002/mrc.2686pmid: 20882515

We report the implementation of our novel rare‐spin homonuclear correlation experiment, namely, Low‐Abundance Single‐transition correlation SpectroscopY (LASSY), for 119/117/115Sn NMR at natural abundance. Our pulse sequence results in diagonal suppressed COSY‐style display and outperforms the optimal homonuclear correlation experiment for rare spins, which involves double quantum evolution (INADEQUATE CR). The new experiment maximizes efficiency both in respect of pulse transformations as well as relaxation effects, and gives rise to a simplified two‐dimensional (2D) spectrum with considerably reduced crowding, exhibiting only one transition in each cross peak, instead of four. Performance optimization of LASSY is carried out in light of the relatively ‘large’ line widths typical of Sn NMR in solution state. The superior performance of the sequence is demonstrated on dimeric tetraorganodistannoxane samples. Copyright © 2010 John Wiley & Sons, Ltd.

Xia, Youlin; Zhu, Qi; Jun, Kyu‐Yeon; Wang, Jingchun; Gao, Xiaolian

doi: 10.1002/mrc.2687pmid: 20957656

Saturation transfer difference (STD)‐NMR has been widely used to screen ligand compound libraries for their binding activities to proteins and to determine the binding epitopes of the ligands. We report herein, a Clean STD‐NMR method developed to overcome false positives (artifacts) observed in the STD‐NMR spectrum due to the power spillover of RF irradiation. The method achieved higher degree of resonance saturation through digital editing of two STD‐NMR spectra to generate a concatenated difference spectrum and three times of sensitivity enhancement for a loose binding complex involving DNA oligonucleotide and an RNA‐binding protein, CUGBP‐1ab (25.2 kDa). The interesting binding characteristics of the complex dCTGTCT–CUGBP1ab were obtained. The method was applied to a mixture of small ligand and bovine serum albumin protein (BSA, 66.3 kDa), and detected the intermolecular contacts at a BSA concentration as low as 0.1 µM, a working concentration useful for the detection of proteins of low solubility at biologically relevant conditions. Copyright © 2010 John Wiley & Sons, Ltd.

Zorin, Vadim; Ciesielski, Filip; Griffin, David C.; Rittig, Michael; Bonev, Boyan B.

doi: 10.1002/mrc.2690pmid: 20941803

Direct observation of J‐couplings remains a challenge in high‐resolution solid‐state NMR. In some cases, it is possible to use Lee–Goldburg (LG) homonuclear decoupling during rare spin observation in MAS NMR correlation spectroscopy of lipid membranes to obtain J‐resolved spectra in the direct dimension. In one simple implementation, a wide line separation‐type 13C‐1H HETCOR can provide high‐resolution 1H/13C spectra, which are J‐resolved in both dimensions. Coupling constants, 1JHC, obtained from 1H doublets, can be compared with scaled 1JθCH‐values obtained from the 13C multiplets to assess the LG efficiency and scaling factor. The use of homonuclear decoupling during proton evolution, LG‐HETCOR‐LG, can provide J‐values, at least in the rare spin dimension, and allows measurements in less mobile membrane environments. The LG‐decoupled spectroscopic approach is demonstrated on pure dioleoylphosphatidylcholine (DOPC) membranes and used to investigate lipid mixtures of DOPC/cholesterol and DOPC/cholesterol/sphingomyelin. Copyright © 2010 John Wiley & Sons, Ltd.

Martin, Gary E.; Hilton, Bruce D.; Moskau, Detlef; Freytag, Nicolas; Kessler, Klemens; Colson, Kim

doi: 10.1002/mrc.2691pmid: 21072790

Long‐range 1H15N heteronuclear shift correlation experiments at natural abundance are becoming more routinely utilized in the characterization of unknown chemical structures from a diverse range of sources including natural products and pharmaceuticals. Apart from the inherent challenges of the low gyromagnetic ratio and natural abundance of 15N, investigators are also occasionally hampered by having to deal with the wide spectral range inherent to various nitrogen functional groups, which can exceed 500 ppm. Earlier triple resonance cryoprobe designs typically provided 90° 15N pulses in the range of 35–40 µs, which did not allow the uniform excitation of wide F1 spectral ranges for 1H15N GHMBC spectra. We report the results obtained with a newly designed Bruker 600 MHz triple resonance TCI Micro CryoProbe™ using methyl orange as a model compound, in which the 15N resonances are separated by > 450 ppm. Copyright © 2010 John Wiley & Sons, Ltd.

Montalvo‐González, J. Ascención; Iniestra‐Galindo, María Guadalupe; Ariza‐Castolo, Armando

doi: 10.1002/mrc.2693pmid: 21031604

The conformations and relative configurations of 20 amines, classified according to the following labeling scheme, were analyzed. Series a comprised compounds derived from N‐(1‐phenylethyl)cyclohexanamine, b comprised derivatives of N‐(1‐(naphthalen‐2‐yl)ethyl)cyclohexanamine, c comprised derivatives of N‐(diphenylmethyl)cyclohexanamine, and d comprised derivatives of N‐(propan‐2‐yl)cyclohexanamine. The compounds were labeled as follows: 1 indicates cyclohexanamine, 2 indicates 2‐methylcyclohexanamines, 3 indicates 3‐methylcyclohexanamines, 4 indicates 4‐methylcyclohexanamines, and 5 indicates 4‐tert‐butylcyclohexanamines. These compounds were prepared without the use of stereoselective induction and, therefore, all expected stereoisomers were observed. Structural assignments were established by 1H, 13C, and 15N NMR. Copyright © 2010 John Wiley & Sons, Ltd.

Filippov, A. V.; Rudakova, M. A.; Munavirov, B. V.

doi: 10.1002/mrc.2694pmid: 21031608

Sphingomyelin (SM) is an important lipid of eukaryotic cellular membranes and neuronal tissues. We studied lateral diffusion in macroscopically oriented bilayers of synthetic palmitoylsphingomyelin (PSM) and natural sphingomyelins of egg yolk (eSM), bovine brain (bSM) and bovine milk (mSM) by pulsed field gradient NMR (PFG NMR) in the temperature range 45–60 °C. We found that the mean values of lateral diffusion coefficients (LDCs) of SMs are 1.9‐fold lower compared with those of dipalmitoylphosphatidylcholine (DPPC), which is similar in molecular structure. This discrepancy could be explained by the characteristics of intermolecular SM interactions. The LDCs of different SMs differ: egg SM is most similar to PSM; both of them have a 10% higher LDC value compared with the other two natural SMs. Besides, all natural SMs show a complicated form of the spin‐echo diffusion decay (DD), which is an indicator of a distribution of LDC values in bilayers. This peculiarity is explained by the broad distributions of hydrocarbon chain lengths of the natural SMs studied here, especially mSM and bSM. We confirmed the relationship between chain length and LDC in the bilayers by computer analysis of a set of 1H NMR spectra obtained by scanning the value of the pulsed field gradient. There is a correlation between lower LDC values and SM molecules with longer acyl chains. The most probable mechanisms by which long‐chain SM molecules decrease their lateral diffusion relative to the average value are protrusion into the other side of the bilayer or lateral separation into areas that diverge with their LDCs. Copyright © 2010 John Wiley & Sons, Ltd.

Kildahl‐Andersen, Geir; Nytoft, Hans Peter; Johansen, Jon Eigill

doi: 10.1002/mrc.2688pmid: 20882514

The full 1H and 13C NMR chemical shift assignment of 2α‐methyl‐17α(H),21β(H)‐hopane is presented. This compound is formed in mature sediments from biogenic sources of 2β‐methyl‐17β(H),21β(H)‐hopanoids, which include several cyanobacteria. In addition, full 1H and 13C NMR chemical shift data of all four 17,21 isomers of 3β‐methylhopane have been assigned. The thermodynamically most stable 3β‐configuration corresponds to that found in bacterial sources. The data presented here suggest minor corrections to the 13C chemical assignments reported earlier for 17α(H)‐hopanes. Moreover, spectral evidence indicates an unexpected ring‐D boat conformation of 17α(H),21α(H)‐hopanes, which may serve to explain the steric strain reported for this isomer. Copyright © 2010 John Wiley & Sons, Ltd.

Ai, Yong; Yang, Guangzhong; Liu, Jianchao; Chen, Yu; Liu, Lu; Lei, Xinxiang

doi: 10.1002/mrc.2689pmid: 20941805

Five new 2‐(amino/aroxy)‐5‐methylpyrimido(5,4‐c)quinolin‐4(3H)‐one derivatives have been designed and synthesized via an aza‐Wittig reaction, and the structure elucidation was accomplished using extensive 1D (1H, 13C) and 2D NMR spectroscopic studies (COSY, HSQC and HMBC experiments). Copyright © 2010 John Wiley & Sons, Ltd.