A high field proton magnetic resonance study of the solution conformation of thromboxane B2

1980 ◽  
Vol 58 (11) ◽  
pp. 1111-1117 ◽  
Author(s):  
George Kotovych ◽  
Gerdy H. M. Aarts
Keyword(s):  
Magnetic Resonance ◽  
High Field ◽  
Double Resonance ◽  
Relaxation Times ◽  
Chair Conformation ◽  
Rotational Correlation Time ◽  
Coupling Constants ◽  
Solution Conformation ◽  
Dipolar Relaxation ◽  
Rotational Correlation

The solution conformation of thromboxane B2 (TXB2) has been studied using high-field nuclear magnetic resonance techniques. In CDCl3, both anomers are present in solution with 76% 11α-OH TXB2 and 24% 11β-OH TXB2. In CD3OD, the predominant anomer is 11β-OH TXB2 (80%) while the concentration of 11α-OH TXB2 is 20%. The proton resonances were assigned at 400 MHz using double resonance techniques. The analysis of the vicinal coupling constants indicates that the six-membered ring is present in solution in a chair conformation with both of the aliphatic side chains equatorial. Proton longitudinal relaxation times were measured at 25 °C in CDCl3 for H-2, H-11β, H-12, H-13, H-14, and H-17 to H-19, both at 200 MHz and at 400 MHz. From the frequency dependence of these dipolar relaxation times, the rotational correlation times were evaluated. Within experimental error, all of the values are similar in magnitude (~ 2.0 × 10−10 s) indicating that this is the molecular rotational correlation time.

The solution conformation of prostacyclin as determined by high field proton magnetic resonance techniques

1980 ◽  
Vol 58 (10) ◽  
pp. 974-983 ◽  
Author(s):  
George Kotovych ◽  
Gerdy H. M. Aarts ◽  
Tom T. Nakashima ◽  
Glen Bigam
Keyword(s):  
Magnetic Resonance ◽  
Correlation Time ◽  
Proton Magnetic Resonance ◽  
Double Resonance ◽  
Relaxation Times ◽  
Segmental Motion ◽  
Solution Conformation ◽  
Nmr Spectrum ◽  
H Nmr ◽  
The Difference

The proton magnetic resonance (1H nmr) spectrum at 400 MHz of prostacyclin at pH 10.4 in glycine buffer has been completely analyzed utilizing homonuclear double resonance, inversion recovery, and difference nOe experiments. The spectral analysis shows that the two protons at C-4 are non-equivalent even though they are removed from the asymmetric centres at C-8 and C-9 by five bonds. The difference nOe measurements verify the configuration at C-5.Proton longitudinal relaxation times (T1) were measured at 400 and 200 MHz. From the T1 frequency dependence, effective rotational correlation times ranging from 2.3 × 10−10 to 3.0 × 10−10 s were calculated for H-5, H-9, H-11, and H-15. This indicates that the portion of the molecule encompassed by these protons has a longer correlation time than is observed for the C-2 and the C-17 to C-19 protons, for which the average correlation time is 1.2 × 10−10 s. Hence the aliphatic side chains have more segmental motion.

scholarly journals NMR solution conformation of heparin-derived tetrasaccharide

1996 ◽  
Vol 318 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Dmitri MIKHAILOV ◽  
Kevin H. MAYO ◽  
Ioncho R. VLAHOV ◽  
Toshihiko TOIDA ◽  
Azra PERVIN ◽  
...  
Keyword(s):  
Chair Conformation ◽  
Coupling Constants ◽  
Solution Conformation ◽  
1H And 13C Nmr ◽  
Small Deviations ◽  
J Coupling Constants ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects ◽  
Dynamics Simulations ◽  
Ring Conformations

The solution conformation of the homogeneous, heparin-derived tetrasaccharide ΔUA2S(1 → 4)-α-d-GlcNpS6S(1 → 4)-α-l-IdoAp2S(1 → 4)-α-d-GlcNpS6S (residues A, B, C and D respectively, where IdoA is iduronic acid) has been investigated by using 1H- and 13C-NMR. Ring conformations have been defined by J-coupling constants and inter-proton nuclear Overhauser effects (NOEs), and the orientation of one ring with respect to the other has been defined by inter-ring NOEs. NOE-based conformational modelling has been done by using the iterative relaxation matrix approach (IRMA), restrained molecular dynamics simulations and energy minimization to refine structures and to distinguish between minor structural differences and equilibria between various ring forms. Both glucosamine residues B and D are in the 4C1 chair conformation. The 6-O-sulphate group is oriented in the gauche–trans configuration in the D ring, whereas in the B ring the gauche–gauche rotomer predominates. Uronate (A) and iduronate (C) residues are mostly represented by 1H2 and 2S0 twisted boat forms, respectively, with small deviations in expected coupling constants and NOEs suggesting minor contributions from other A and C ring conformations.

Structural studies of digitoxin and related cardenolides by two-dimensional NMR

1990 ◽  
Vol 68 (2) ◽  
pp. 272-277 ◽  
Author(s):  
Torbjörn Drakenberg ◽  
Peter Brodelius ◽  
Deane D. McIntyre ◽  
Hans J Vogel
Keyword(s):  
Nmr Spectroscopy ◽  
Nmr Spectra ◽  
Chair Conformation ◽  
Coupling Constants ◽  
Two Dimensional ◽  
Structural Studies ◽  
Solution Conformation ◽  
Phase Sensitive ◽  
Multiple Relay ◽  
C Nmr

The 1H and 13C NMR spectra of the cardenolides digitoxigenin, digoxigenin, digitoxin, and mono- and bis-digitoxigenin digitoxosides have been completely assigned by two-dimensional NMR spectroscopy. The techniques used include phase-sensitive COSY, multiple relay COSY, and carbon–proton correlation (HETCOR and HMQC) spectra. Various aspects of the solution conformation of the steroid moiety of digitoxin and digoxigenin could be determined from coupling constants and NOE difference experiments and they are indicative of an all-chair conformation. The carbohydrate rings in digitoxin and the mono- and bis-digitoxigenin digitoxosides are also in the chair conformation. Keywords: cardenolides, digitoxigenin, digitoxin, 2-dimensional NMR, conformational analysis.

Conformational dependence of long-range spin-spin coupling constants in 2,6-dichlorobenzylfluoride

1969 ◽  
Vol 47 (19) ◽  
pp. 3688-3690 ◽  
Author(s):  
T. Schaefer ◽  
C. M. Wong ◽  
K. C. Tam
Keyword(s):  
Magnetic Resonance ◽  
Long Range ◽  
Proton Magnetic Resonance ◽  
Resonance Spectrum ◽  
Double Resonance ◽  
Proton Magnetic Resonance Spectrum ◽  
Coupling Constants ◽  
Spin Coupling ◽  
Spin Coupling Constants ◽  
Spin Spin Coupling

Double resonance experiments on the proton magnetic resonance spectrum of 2,6-dichlorobenzylfluoride yield the signs of the long-range coupling constants between the ring protons and the fluorine nuclei and protons in the fluoromethyl group. The signs and magnitudes of the long-range couplings are discussed in terms of their dependence on the conformation of the fluoromethyl group.

Appunti dal Congresso ASNR di Vancouver Risonanza Magnetica a 3 Tesla

2002 ◽  
Vol 15 (6) ◽  
pp. 779-785
Author(s):  
A. Bacci
Keyword(s):  
Magnetic Field ◽  
Magnetic Susceptibility ◽  
Magnetic Resonance ◽  
Chemical Shift ◽  
Spatial Resolution ◽  
High Field ◽  
Mr Angiography ◽  
Relaxation Times ◽  
Signal Noise ◽  
Noise Ratio

The theme of this year's 40th Congress of the American Society of Neuroradiology was 3 Tesla magnetic resonance. For many years, research into the use of magnetic resonance systems with 3 T magnets mainly focused on spectroscopy and functional magnetic resonance. More recent studies also used 3 T magnets for MR diagnosis, trying to optimize sequences for both anatomic imaging and for MR angiography and diffusion on the basis of protocols currently adopted with 1.5 T magnets1–3. The use of higher magnetic fields improves the signal/noise ratio and the chemical-shift sensitivity thereby enhancing spatial resolution (supported by the higher signal/noise ratio) and increasing the reliability of spectroscopy and functional MR imaging. The major technical problems encountered with 3 T systems are the increased number of artefacts due to magnetic sensitivity and chemical shift, the increase in tissue heating potential and the longer T1 longitudinal relaxation times. The main advantages of high magnetic field resonances are the higher signal/noise ratio, greater spectra dispersion, improved image resolution, faster acquisition times and greater sensitivity to differences in magnetic susceptibility. The drawbacks include a lower signal/noise ratio in relation to artefacts caused by magnetic susceptibility, longer T1 relaxation times, shorter T2 and T2* relaxation times, convergent tissue relaxation times, increased absorption of RF energy and a more inhomogeneous B1 signal. The advantages and limitations of higher magnetic field magnets have already been encountered at each stage in the development of MR technology. Once again, the best strategies need to be devised for the use of these new systems. Briefly, the increased signal produced by high field magnets (3 T) offers different advantages. In conventional diagnosis, the spatial resolution of the image is improved or acquisition times shortened, or when contrast is poor with current techniques as in functional MR or spectroscopy. Even the increase in artefacts due to magnetic susceptibility and chemical shift can be exploited advantageously. For example, the enhanced magnetic susceptibility produces a greater loss of signal intensity in sequences with gadolinium bolus perfusion, thereby improving assessment of brain haemodynamics and tissue vitality for a rational selection of candidates for stroke therapy and surgery. Studies were presented from different stroke centres in the United States using protocols comprising sequences for conventional anatomical investigation, weighted diffusion sequences, MR angiography and bolus perfusion. Image quality was equivalent or superior to that obtained with 1.5 T systems, especially angiographic sequences which were improved and faster with easier identification of the occluded branch. It was also demonstrated that the examination can be performed while the patient is receiving an infusion of thrombolytic drugs with real time monitoring of the pharmaceutical effect on the thrombosis. A group of researchers then presented their findings studying patients with an 8T MR system23–25. Exposure to such a high magnetic field was well tolerated and the study focused on evaluation of the small cerebral vessels exploiting sensitivity differences in blood oxygenation as deoxyhaemoglobin is paramagnetic and the effected of magnetic susceptibility exaggerated by such a high field. Using inhomogeneous local fields with gradient-echo images together with the signal/noise ratio of an 8 T system, minute cerebral vessels with a diameter of around 200 micron could be visualized. What emerged from the Congress presentations was that we can no longer be satisfied with the MR systems in use today when examinations which are currently long and cumbersome can be carried out more quickly, often with real time results and much shorter processing times. The impression was that the 1.5 T MR systems most of us use will soon be as obsolete as the 0.5 T systems and neuroradiologists' work will be increasingly shifted from morphological investigation to functional analysis, entailing new expertise. My only concern is the exposure of patients to such high magnetic fields, fearing the biological effects, especially when follow-up examinations have to be repeated. I hope that patients' welfare will not be disregarded in the search for ever greater morphological detail and that the new systems will be used when their true worth is of real benefit.

Molecular Determinants for Drug-Receptor Interactions. 6. Proton 500 MHz NMR Spectra of the Narcotic Antagonists Naloxone and Naltrexone by Two-Dimensional 1H–1H Chemical Shift Correlation Spectroscopy

1986 ◽  
Vol 41 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Bruno Perly ◽  
Giuseppe C. Pappalardo ◽  
Antonio Grassi
Keyword(s):  
Nmr Spectra ◽  
Chemical Shifts ◽  
Relaxation Times ◽  
Chair Conformation ◽  
Correlation Spectroscopy ◽  
Coupling Constants ◽  
Piperidine Ring ◽  
Two Dimensional ◽  
Spectral Parameters ◽  
Narcotic Antagonists

The full analysis of the 1H NMR spectra of naloxone and naltrexone (hydrochloride salts, in 2H2O solution) was performed by using an high-frequency (500 MHz) spectrometer and the recent technique of two-dimensional (2D ) homonuclear shift spectroscopy. The 1H-1H connectivities allowed detection of correlated resonances and assignments of multiplets. The shapes of the contour levels of the COSY 45 spectra were also used to check the relative signs of coupling constants. The refinement of spectral parameters of some component spin-systems of the complex spectra was performed by computerized iterative simulation of patterns.The spectral analysis provided proton coupling constants that allowed to establish a slightly distorted-chair conformation of the piperidine ring in both compounds.The magnetic non-equivalence found for the protons bonded to C-17 atom (part of the N-alkyl fragment) was found to be larger in naltrexone than in the analogous naloxone. This fact, while no significant differences were observable in the chemical shifts of corresponding protons of the rigid molecular backbone of the two narcotic antagonists under study, was assigned to smaller degree of internal conformational flexibility of the N-methylcyclopropyl group in naltrexone with respect to that of the N-methylallyl group in naloxone.The above findings appeared in good agreement with our previously proposed views based on results from 13C relaxation times studies, which suggested the possible correlation of the motional rates of the N-methyl-R group to the pharmacological activity of antagonist compounds. This would consist in a direct correlation between decreasing flexibility of the N-bonded fragment and increasing antagonistic potency.

39K and 13C nuclear magnetic resonance studies of the potassium cation – dibenzo-30-crown-10 complex in solution

1987 ◽  
Vol 65 (7) ◽  
pp. 1684-1687 ◽  
Author(s):  
Christian Detellier ◽  
Marc Robillard
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Relaxation Times ◽  
Potassium Thiocyanate ◽  
Coupling Constants ◽  
Potassium Cation ◽  
Thiocyanate Complex ◽  
Quadrupolar Coupling ◽  
13C Nuclear Magnetic Resonance ◽  
Nuclear Magnetic

The structure and microdynamics in solution of the dibenzo-30-crown-10–potassium thiocyanate complex have been studied by 39K and 13C nuclear magnetic resonance. In the four solvents studied (nitromethane, acetonitrile, acetone, and pyridine), the large crown ether wraps around the potassium cation and expels the conjugate anion and the solvent molecules from the cation coordination sphere. Measurements of 39K quadrupolar and 13C dipole–dipole relaxation times in acetone-d6 gave the effective correlation time of the complex and the 39K quadrupolar coupling constant (1.4 ± 0.3 MHz). The comparison between 23Na and 39K quadrupolar coupling constants for the complexes Na+–dibenzo-24-crown-8 and K+–dibenzo-30-crown-10 showed that the electric field gradients at the metal nucleus sites are quasi identical [Formula: see text] in the two complexes.

scholarly journals NMR solution conformation of heparin-derived hexasaccharide

1997 ◽  
Vol 328 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Dmitri MIKHAILOV ◽  
J. Robert LINHARDT ◽  
H. Kevin MAYO
Keyword(s):  
Energy Minimization ◽  
Conformational Stability ◽  
Chair Conformation ◽  
Coupling Constants ◽  
Solution Conformation ◽  
Explicit Solvent ◽  
J Coupling Constants ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects ◽  
A Minor

The solution conformation of homogeneous, heparin-derived hexasaccharide (residues A, B, C, D, E, F) has been investigated by using 1H-NMR spectroscopy. Intra-ring conformations have been defined by J-coupling constants and inter-proton nuclear Overhauser effects (NOEs), and the orientation of one ring with respect to the other has been defined by inter-ring NOEs. NOE-based conformational modelling has been done by using the iterative relaxation matrix approach (IRMA), restrained energy minimization to refine structures and to distinguish between minor structural differences and equilibria between various intra-ring forms. All glucosamine residues B, D and F are in the 4C1 chair conformation. The uronate (A) residue is mostly represented by the 1H2 form, whereas internal iduronates (C and E) exist in equilibrium between the chair and skewed boat forms. Deviations in some NOEs indicate a minor contribution of the 2H1 form to the A ring. Glycosidic dihedral angles, which define the overall oligosaccharide conformation, were further refined by combining in vacuo energy map calculations and restrained energy minimization in explicit solvent water. Conformational stability was further assessed by subjecting NOE and IRMA-derived structures to 600 ps of unrestrained molecular dynamics in explicit solvent.

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