NOESY enhancement spectroscopy

Figure 3.1 The various time periods in a two-dimensional NMR experiment. Nuclei are allowed to approach a state of thermal equilibrium during the preparation period before the first pulse is applied. This pulse disturbs the equilibrium ptolariza-tion state established during the preparation period, and during the subsequent evolution period the nuclei may be subjected to the influence of other, neighboring spins. If the amplitudes of the nuclei are modulated by the chemical shifts of the nuclei to which they are coupled, 2D-shift-correlated spectra are obtained. On the other hand, if their amplitudes are modulated by the coupling frequencies, then 2D /-resolved spectra result. The evolution period may be followed by a mixing period A, as in Nuclear Overhauser Enhancement Spectroscopy (NOESY) or 2D exchange spectra. The mixing period is followed by the second evolution (detection) period) ij.

NOESY/ROESY nuclear Overhauser enhancement spectroscopy... 

Nuclear Overhauser enhancement spectroscopy (NOESY) experiments play a very important role in structural studies in quinolizidine derivatives. For instance, the endo-type structure of compound 28 was proven by the steric proximity of the H-3a and H-12a protons according to the NOESY cross peak, while the spatial proximity of the H-6f3 and H-8/3 protons reveals that tha A/B ring junction has a /ra t-stereochemistry. Similarly, compound 28 could be distinguished from its regioisomer 29 on the basis of the NOESY behavior of its H-13 atom <1999JST153>. 

The relative stereochemistry of hyperaspine 93 was determined by 2-D NMR spectroscopic and mass spectrometry (MS) methods. It has a m-fused bicyclic conformation 93a <2001TL4621>. The trans-fused one is disfavored by an axial pentyl group at C-8 and by a destabilizing dipole-dipole interaction between the N- and O-atoms, which does not exist in the alternative //.(-conformation. The geminal coupling constant of C( 1 )H2 in 93 (11.0 Hz), and that of its 6-hydroxy derivative (11.2 Hz), indicates that they exist preferentially in / //-conformations, whereas their 6-epimers adopt trans-conformations (9.3 and 8.4 Hz, respectively) <2005EJ01378>. Nuclear Overhauser enhancement spectroscopy (NOESY) studies also confirmed the stereochemistry of 93 by the marked nuclear Overhauser effect (NOE) correlation between H-3 and H-4a <20030L5063>. 

Total assignment of the H and 13C NMR chemical shifts as well as the relative configuration of the Diels-Alder adducts 33-35 was accomplished with the help of 2D (111-111 COSY, H-111 NOESY (NOESY = nuclear Overhauser enhancement spectroscopy), H- C XHCORR (XHCORR = nucleus X-hydrogen correlation), H-13C COLOC) and NOE difference spectroscopy <1996JHC697>. 

Assignment of the isotropically shifted signals observed for the CuNiSOD example discussed in the previous paragraph has been achieved by means of anion titrations (not discussed here) and nuclear Overhauser enhancement spectroscopy (NOESY), to be discussed next. In Figure 3.24B the CuNiSOD active site is depicted with histidine nitrogens and protons identified for the discussion of the NOESY results. The copper(II) ion is coordinated to the N ligand atoms of his46... 

The stereochemistry of the obtained acetals was confirmed by nuclear overhauser enhancement spectroscopy (NOESY) measnrement in NMR spectra. 

Nuclear Overhauser enhancement spectroscopy ( H- H NOESY and NOE) experiments show only the TTC isomer in equilibrium with the TTT isomer for 6,8-dinitro-BIPS [36,55] and 6-nitro,8-bromo-BIPS. The TTC form dominates the equilibrium. Spectral broadening for several proton resonances in the spectra of 6,8-dinitro-BIPS and 6-nitro,8-bromo-BIPS indicate a rapid exchange between these two isomeric forms. The activation energy for this isomerisation is reported to be 43.6 kJ mol and the energy difference between the the TTC and TTT forms is 4.6 kJ mol [55]. 

The most important two-dimensional NMR experiments for solving stmctural problems are COSY (Correlation SpectroscopY), NOESY (Nuclear Overhauser Enhancement SpectroscopY), HSC (Heteronuclear Shift Correlation) and TOCSY (Total Correlation SpectroscopY). Most modem high-held NMR spectrometers have the capability to routinely and automatically acquire COSY, NOESY, HSC and TOCSY spectra. 

Aryl derivatives of thieno[3,2-f]pyridines, 36 and 37, have been the subject of two-dimensional (2-D) NMR studies. Phase-sensitive nuclear Overhauser enhancement spectroscopy (NOESY) and correlation spectroscopy (COSY) experiments confirm the nonplanar conformation of the two aromatic ring systems <1999SAA1035>. 

Record the 2-D H- H nuclear Overhaiiser enhancement spectroscopy (NOESY) spectrum (Braun et al., 1998, pp. 405-408). 

Couplings don t necessarily have to occur through bonding. Protons that are close to each other in space may be observed as cross-peaks in a nuclear Overhaiiser enhancement spectroscopy (NOESY) spectrum. Thus, the more sensitive NOESY experiment proves to be an alternative technique to HMBC for determination of some linkages within an anthocyanin. When a sugar is attached to the aglycone 3-po-... 

NMR nuclear magnetic resonance NO-heme nitrosylheme NOESY nuclear Overhauser enhancement spectroscopy... 

The spirobenzoxazepine 28 was studied by 2-D and nuclear Overhauser enhancement Spectroscopy (NOESY) NMR and X-ray crystallography, and in both cases the same chair conformation, 28, was formed (See Figure 5). The authors conclude that this compound 28 is a semirigid scaffold, able to present various substituents without undergoing hydrophobic collapse, and 28 behaves structurally as a privileged structure <2004TL1051>. 

Correlation spectroscopy (COSY), nuclear overhauser enhancement spectroscopy (NOESY), I-D NOE, and HPLC techniques were utilized in the identification of three trapped products formed from coupling of the generated C4-centered radical of artemisinin with manganese(n) tetraphenylporphorin <2001AGE1954>. 

H and 13C NMR techniques have widely been used to determine the configuration of new dioxepins and dithiepins and to elucidate the constitution and conformation of new naturally occurring substances. For example, the configuration of oximes 14 was determined by H and 13C correlated spectra, correlation spectroscopy (COSY), nuclear Overhauser enhancement spectroscopy (NOESY), heteronuclear correlation (HETCOR) spectroscopy, and hetero-nuclear multiple bond correlation (E1MBC) spectroscopy <1998CCA557>. 

A novel cysteine derivative, spongiacysteine, was isolated recently from marine sponge. It was converted to lactone 4 by reaction with 2,4,6-trichlorobenzoyl chloride, 4-dimethylaminopyridine (DMAP), and triethylamine. Selected nuclear Overhauser enhancement spectroscopy (NOESY) correlation and coupling constants are given <2004CL1262>. 

Notably, two isomeric products can be generated. The usual infrared (IR) and mass spectra as well as H and 13C NMR chemical shifts could not define which isomer was formed. The authors used different NMR techniques, such as 2-D heteronuclear multiple bond correlation (HMBC) experiments and phase-sensitive nuclear overhauser enhancement spectroscopy (NOESY) measurements to elucidate the product s structure. 

The bridged 15 exists as a 3 1 mixture of invertomers at 25 °C and the relative configuration of the stereocenters (C-5, C-6, and G-9) has been determined by one-dimensional nuclear Overhauser enhancement spectroscopy (1-D NOESY) experiments <2004TA3181>. 

High resolution multidimensional NMR experiments can provide the dendrimer chemist with a wealth of additional information extending far beyond the determination of the molecular structure. In the interpretation of (2D)-NOESY (NOESY=nuclear Overhauser enhancement spectroscopy) spectra, a knowledge of the spatial interrelationships between protons in different parts of the dendrimer scaffold can be acquired from proton-proton NOE interactions. At the same time, the prevailing conformation of the dendritic branches in the solvent used can be deduced from this information. Furthermore, studies of dendrimer/sol-vent interactions and the influence of solvent on the spatial structure of the dendrimer are also possible [22]. Thus the information content of such NMR experiments resembles that of small-angle scattering experiments on dissolved dendrimers (see Section 7.6). 

The vast literature associated with flavanoid chemistry precludes a discussion here but two valuable reviews have been published. The first reviews a number of spectroscopic techniques used for flavonoid analysis, with a strong emphasis on NMR spectroscopy (plus also mass spectrometry, vibrational spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, X-ray crystallography, and circular dichrosim (CD)) . The second review deals with NMR methods that have been successful in the characterization of phenolic acids and flavonoids from plant extracts that have not been separated or isolated as single components. The emphasis of the article is 2-D NMR methodology and a variety of experiments such as total correlated spectroscopy (TOCSY), COSY, nuclear Overhauser enhancement spectroscopy (NOESY) and heteronuclear multiple quantum correlation (HMQC) are discussed . 

NOESY/STD Nuclear Overhauser Enhancement spectroscopy/saturation transfer difference... 

A 2002 review by Reynolds and Enriquez describes the most effective pulse sequences for natural product structure elucidation.86 For natural product chemists, the review recommends HSQC over HMQC, T-ROESY (transverse rotating-frame Overhauser enhancement) in place of NOESY (nuclear Over-hauser enhancement spectroscopy) and CIGAR (constant time inverse-detected gradient accordion rescaled) or constant time HMBC over HMBC. HSQC spectra provide better line shapes than HMQC spectra, but are more demanding on spectrometer hardware. The T-ROESY or transverse ROESY provides better signal to noise for most small molecules compared with a NOESY and limits scalar coupling artefacts. In small-molecule NMR at natural abundance, the 2D HMBC or variants experiment stands out as one of the key NMR experiments for structure elucidation. HMBC spectra provide correlations over multiple bonds and, while this is desirable, it poses the problem of distinguishing between two- and three-bond correlations. 

We described the basic aspects of NOESY in Section 10.1 as an introductory example of a 2D experiment. NOESY is very widely used in measuring macro-molecular conformation, as we see in Chapter 13. However, as shown in Fig. 8.4, the H— H nuclear Overhauser enhancement 17 varies from its value of +0.5 in small molecules to a limiting value of — 1 in large polymers with very long Tc, and at intermediate values of rc the NOE may vanish. An alternative is to use the NOE measured in the rotating frame, as this quantity is always positive. By analogy to NOESY, this technique has the acronym ROESY (rotating frame Overhauser enhancement spectroscopy),... 

Laurie was one of the first to apply two-dimensional (2D) NMR to carbohydrates. With students Subramaniam Sukumar and Michael Bernstein, and visiting scientist Gareth Morris, he demonstrated and extended the application of many of the directly observed 2D NMR techniques of the time. These included the homo- and hetero-nuclear 2D /-resolved techniques, delayed proton /-resolved NMR that allowed broad resonances to be suppressed, for example, those of dextran in the presence of methyl /Lxvlopyranoside. proton-proton chemical shift correlation spectroscopy (COSY), nuclear Overhauser enhancement spectroscopy (NOESY), proton-carbon chemical shift correlation (known later as HETCOR), and spin-echo correlated spectroscopy (SECSY). Trideuteriomethyl 2,3,4,6-tetrakis-<9-trideuterioacetyl-a-D-glucopyranoside served as a commonly used model compound for these studies. 

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