Heteronuclear NOE in the solid state

A series of small molecules and polymers was examined in order to investigate the heteronuclear NOE effect in solids. Contrary to a previously reported interpretation it was found that caution has to be used in interpreting NOE rates purely in terms of correlation times. The NOE rate of a methyl group was not solely dependent upon correlation times but also the distance (r⁻⁶) from the nearest methyl neighbour.     

Carbon-13 spin-lattice relaxation times and nuclear overhauser enhancements in some simple fluorocarbons

Carbon-13 spin-lattice relaxation times (T₁) and ¹³C-{¹⁹F} nuclear Overhauser enhancement (NOE) factors have been measured for some simple fluorocarbons by pulse-Fourier transform methods—‘progressive saturation’ and ‘dynamic Overhauser enhancement’. The NOE factors are shown to be large for ¹³C with directly bonded fluorines, and the values for T₁ and the NOE factors are similar to those obtained elsewhere on the corresponding hydrocarbons.     

Application of selective 13C?{1H} nuclear overhauser effects with low-power 1H irradiation in carbon-13 NMR spectroscopy

The feasibility of the application of selective ¹³C? {¹H} nuclear Overhauser effect (NOE) measurements to organic structural analysis in ¹³C NMR spectroscopy has been investigated at 25 MHz using citraconic anhydride and the methyl ester of pentalenolactone as model compounds. This selective ¹³C? {¹H} NOE technique with single frequency low-power ¹H irradiation should find wide application in the structural elucidation of organic compounds, especially for the reliable assignment of quaternary carbon signals.     

Structural analyses of mannose pentasaccharide of high mannose type oligosaccharides by 1D and 2D NMR spectroscopy

NMR spectroscopy is a very important and useful method for the structural analysis of oligosaccharides, despite its low sensitivity. We first applied conventional measuring methods, 2D DQF COSY, ¹H–¹³C HSQC, and ¹H–¹³C HMBC, and also the Double Pulsed Field Gradient Spin Echo (DPFGSE)‐TOCSY and DPFGSE‐NOESY/ROESY techniques to analyze a branched mannose pentasaccharide as a model of high mannose type N‐glycans in natural abundance. The NMR spectra of the model compound are very complex and difficult to analyze owing to overlapping signals. The superior selective irradiation capability of the DPFGSE technique is useful for fine structural and conformational analyses of such complex oligosaccharides. We here introduce a novel technique called DPFGSE‐Double‐Selective Population Transfer (SPT)‐Difference and DPFGSE‐NOE/ROE‐SPT‐Difference spectroscopy. The DPFGSE‐Double‐SPT‐Difference method involves irradiation of two peaks from one proton and the subtraction of higher and lower peaks from each spectrum. The DPFGSE‐NOE/ROE‐SPT‐Difference method involves the transfer of the magnetization polarized by NOE/ROE from the nuclei to the spin‐coupled nuclei through scalar spin–spin interaction using the SPT method. Even if the signals in the NMR spectra overlap, each signal can be accurately assigned. In particular, DPFGSE‐NOE/ROE‐SPT‐Difference is very useful for identifying sugar connectivity. Copyright © 2012 John Wiley & Sons, Ltd.     

Indoles et quinoléines dérivés de la thiochromannone-3

The synthesis from 3-thiochromanone of indole and quinoline derivatives is reported. The structures of the compounds obtained, which are analogs of carcinogenic nitrogen polycycles, were determined by means of mass spectrometry and high resolution NMR spectrometry. In the latter case, Nuclear Overhauser Enhancements (NOE) allow the unequivocal determination of structures. Furthermore, direct (or“through space”) ¹H-¹H couplings are reported and related to the NOE.     

Direct structure determination of the self-condensation product of 1-phenylpentane-2,4-dione using T1 and NOE measurements from 13C NMR spectroscopy

The nuclear Overhauser effect (NOE) is known to depend on molecular dynamics and structure. However, in some cases the values obtained for selective homonuclear and heteronuclear NOE are much too small, considering that the nuclei involved are located within a short distance of each other in space. A quantitative treatment of the NOE values allows a clear explanation of this apparent anomaly, and allows the possibility of using T₁ and NOE values measured with broad-band proton irradiation. The corresponding relationship is useful for solving many structural problems in organic chemistry, and has the great advantage of employing the typical high resolution of fully decoupled spectra. The method was used in this work for the structure determination of the self-condensation product of 1-phenylpentane-2,4-dione, and it was concluded that the previous assignment of the ¹³C NMR spectrum was erroneous. An independent proof of the new assignment is given using the selective collapse of the fine structure under low-power irradiation of the methyl protons.     

The configuration of β-halogenoenamines. The use of a new procedure for NOE measurements

The configurations of 16 different β-halogenoenamines have been determined using the proton NOE effect, and the same results were obtained as when the ²J(CH) coupling constants were used. A new procedure called the ‘repetitive shift frequency’ is presented for the NOE determinations which allows better reproducibility and improves the precision.     

Gradient-purged isotope filter experiments for the detection of bound water in proteins

A combination of gradient-purged isotope-filtered NMR experiments is presented, which allows for the detection of long-lived bound water molecules in proteins. The discrimination of direct water–protein exchange from NOE effects between bound water and protein protons is achieved by NOE/ROE cancellation during the mixing time in one of the otherwise identical experiments. The method was applied successfully to ¹³C/¹⁵N-labelled serine protease PB92, and allowed for the identification of 22 protein–water NOEs in this 269-residue enzyme.     

Natural abundance nitrogen-15 n.m.r. spectroscopy. Spin–lattice relaxation in organic compounds

The small negative magnetogyric ratio (γ) of the ¹⁵N nucleus decreases the efficiency of ¹⁵N? ¹H dipole-dipole relaxation to about 25% of that for an analogous ¹³C nucleus. This may lead to greater competition from other relaxation mechanisms in ¹⁵N n.m.r. and consequent partial or total quenching of the negative nuclear Overhauser effect (NOE). In unfavorable circumstances nulling of the ¹⁵N resonance can occur. Previous ¹⁵N relaxation studies have examined isotopically enriched, low molecular weight compounds. The present study examines several small to intermediate size organic compounds containing nitrogen at natural isotopic abundance. In contrast to some of the earlier studies, ¹⁵N? ¹H dipolar relaxation was found to be dominant for protonated nitrogen atoms, even for two tertiary nitrogens (the tertiary amine nitrogen in 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizine and the oxime nitrogen in 3-methyl-2-pentanone ketoxime). The magnitude of the NOE and the moderate value of T₁ indicate effective dipolar relaxation from neighboring but not directly bonded protons in these cases. Nitro groups were found, as expected, to have predominant contributions from non-dipolar mechanisms, and in one case (2-methyl-2-nitro-1, 3-propanediol) signal nulling (NOE of η = ?1) was observed. The effect of paramagnetic impurities was demonstrated for ethanolamine, which contains a basic nitrogen. In this case T₁^DD(¹⁵N? ¹H) = 4·3 s; added Ni(acac)₂ at 1 × 10^?4 Molar reduced the ¹⁵N T₁ to 0·065 s and consequently the NOE to η = 0.     

A 15N NMR investigation of a series of benzotriazinones and related antitumour heterocycles

A series of 3‐substituted 1,2,3‐benzotriazin‐4‐ones, 1 and 2, were synthesized by standard methods and the ¹⁵N NMR spectra were recorded. All spectra were obtained using the natural abundance of the nitrogen‐15 isotope. The chemical shifts appear in the normal range for N‐1, N‐2 and N‐3 of the triazine ring, and also correlate with the chemical shifts in the spectra of the imidazolotriazinone, 4, and the imidazolotetrazinone, 5. Significantly, the spectra of 1a, 2 and 4, recorded with full NOE, show inversion of the singlet assigned to N‐3, demonstrating that these compounds exist in the tautomeric form shown. The structure of the 4‐iminobenzotriazinone (3) was confirmed by this ¹⁵N NMR analysis. The spectrum shows a signal for the NH‐bearing imino‐nitrogen atom, which is an inverted singlet in the NOE spectrum, whereas the signal from the N‐3 atom of 3 is not inverted in the NOE spectrum. Copyright © 2002 John Wiley & Sons, Ltd.     

Quantitative NMR measurements in copolymers of vinylidene chloride and acrylonitrile: The effect of saturation and varying nuclear Overhauser enhancements

Spin-lattice relaxation times and nuclear Overhauser enhancements (NOE) for ¹³C nuclei in copolymers of acrylonitrile and vinylidene chloride were measured at 20.1 and 67.9 MHz. In the ? CCl₂? region of the spectrum T₁ and NOE values of the various resonances are equal within experimental error and are invariant to changes in composition. The T₁ and NOE values of the ? CCl₂? region, however, are not equal to those of the ? CH? or ? CN region. As a result compositions cannot be calculated by direct comparison of the areas in the ? CCl₂? region and either the ? CH? or the ? CN region. Discrepancies can be corrected for the ? CH? resonances by multiplication of the area by an empirical constant. A similar constant for the ? CN region is composition-dependent at 20.1 and 67.9 MHz. A chemical shift anisotropy mechanism is postulated as important for relaxation of the ? CN resonances. The overall influence of variable T₁ and NOE values on quantitative determination of polymer composition is considered.     

Assay of Aspirin,Ethenzamide and Caffeine Mixture by 13C NMR Spectrometry

¹³C FT NMR method of gated decoupling without NOE was applied in the quantitative analysis of aspirin, ethenzamide and caffeine mixture (antipyretic). Spectra were obtained in pyridine-d⁵, containing anisole as an internal standard and chromium(III) acetylacetonate as a paramagnetic relaxation reagent, The results were generally satisfactory.     

Conformational analyses of α and β (1–6) mannodisaccharides by deuterium substitution effect on relaxation rate and NOE

The study of ¹H differential relaxation rate and NOE using chirally deuterated sugars, revealed the preferred conformation of each α and β (1–6) linkage of oligomannoses in solution.     

Fungal extractives—IV: Structure of a novel sesquiterpene dialdehyde from Lactarius by spectroscopic methods

The complete structure of a sesquiterpene dialdehyde (“velleral”), isolated from Lactarius vellereus and L. pergamenus, has been elucidated by means of IR, UV, ¹³C-NMR spectroscopy, NOE measurements and computer simulation of the ¹H-NMR spectrum.     

Conformation of gallicin,a ten-membered-ring sesquiterpene lactone

Conformation 8 was assigned to gallicin on the basis of NOE effect, variable-temperature ¹H-NMR, LIS and chemical data interpretation.     

Cycloaddition reactions of cephalosporin compounds. XI. 1,3-dipolar cycloaddition reaction of an exo-2-methylenecephem with diphenyldiazomethane

In the 1,3-dipolar cycloaddition reaction of the exo-2-methylenecephem 6 with diphenyldiazomethane the initially formed pyrazolines decompose and spirocyclopropylcephalosporin formation takes place. The structure elucidation with ¹H, ¹³C, ASIS and NOE nmr methods is also described.     

The Stereostructure of Porphyra‐334: An Experimental and Calculational NMR Investigation. Evidence for an Efficient ‘Proton Sponge’

The mycosporine‐like amino acid (MAA) porphyra‐334 ( 1 ) is subjected to extensive ¹H‐ and ¹³C‐NMR analysis as well as to density‐functional‐theory (DFT) calculations. All ¹H‐ and ¹³C‐NMR signals of 1 are assigned, as well as the resonances of prochiral proton pairs. This is achieved by 500‐MHz standard COSY, HMQC, and HMBC experiments, as well as by one‐dimensional (DPFGSE‐NOE) and two‐dimensional (NOESY) NOE experiments. Diffusion measurements (DOSY) confirm that 1 is monomeric in D₂O solution. DFT Calculations yield ¹³C‐NMR chemical shifts which are in good agreement for species 6 which is the imino N‐protonated form of 1 . An exceptionally high proton affinity of 265.7 kcal/mol is calculated for 1 , indicating that 1 may behave as a very powerful ‘proton sponge’ of comparable strength as synthetic systems studied so far. Predictions of ¹³C‐NMR chemical shifts by the ‘NMRPredict’ software are in agreement with the DFT data. The absolute configuration at the ring stereogenic center of 1 is concluded to be (S) from NOE data as well as from similarities with the absolute configuration (S) found in mycosporine‐glycine 16 . This supports the assumption that 1 is biochemically derived from 3,3‐O‐didehydroquinic acid ( 17 ). The data obtained question the results recently published by a different research group claiming that the configuration at the imino moiety of 1 is (Z), rather than (E) as established by the here presented study.     

Conformational analysis: 3JHCOC and 3JHCCC Karplus relationships for methylene 1H nuclei

NAMFIS (NMR Analysis of Molecular Flexibility In Solution) was applied to 1‐[2‐(benzyloxy)phenyl]ethanone using quantitative ¹H‐¹H NOE distances and ³J proton‐carbon coupling constant (CC) restraints for averaged methylene proton ³J_HCOC and ³J_HCCC pathways H₂‐³J‐X imposed by density functional theory‐generated Karplus relationships. Comparison of the NOE‐only versus the NOE + CC conformational selections illustrates that the experimentally measured average ³J coupling constants of methylene protons can be used for solution conformational analysis, potentially valuable in the study of small‐molecule drugs and natural products which lack the typically studied H₁‐³J‐X Karplus relationships. Copyright © 2015 John Wiley & Sons, Ltd.     

Identification of modified natural porphyrin isomers: 1H and 13C NMR assignments by NOESY and reverse heteronuclear shift correlation

The efficiency of two-dimensional homonuclear ¹H ¹H NOE spectroscopy in characterizing and fully assigning the ¹H NMR spectra of several isomers of meso- or ring-substituted deuteroporphyrins is demonstrated. The carbon resonances of the skeleton and the substituents were fully assigned using two-dimensional reverse heteronuclear shift correlation spectroscopy.     

neo‐Clerodane Diterpenoids from the Aerial Part of Scutellaria barbata

Three new neo‐clerodane diterpenoids, barbatellarines C–E ( 1 – 3 ), were isolated from the CHCl₃‐soluble fraction of the aerial part of Scutellaria barbata. Their chemical structures were elucidated by detailed analysis of NMR and MS data. Compounds 1 and 2 were C(13) epimers, which was confirmed by an NOE difference experiment and the NOESY spectrum. The relative configuration was determined on the basis of the ¹H‐NMR J‐value and NOE data, while the absolute configuration of the previously isolated analogue, barbatellarine B ( 4 ), as a representative member of the group, was assigned by CD analysis.