NOE correlated spectroscopy

The stereochemistry of compounds 60-63 was fully determined by various NMR techniques such as nuclear Overhauser effect (NOE), correlation spectroscopy (COSY), and nuclear Overhauser enhancement spectroscopy (NOESY) <1996MRC52>. The conformation of the 2,3-butanedione trimer 64 and similar compounds has been examined by NMR at —90°C <2000T10005>. 

Nuclear magnetic resonance NOE correlated spectroscopy Nuclear Overhauser effect Chair and Transoid Boat and Cisoid Chair and Cisoid Boat and Transoid Dimethyl sulfoxide tert-Butyldimethylsilyl chloride N, A -Dimethylpropyleneurea 10-Camphorsulfonic acid... 

Eor a macromolecule such as a large protein, the steps in characterization involve, first, identification of the spin systems present, using correlated spectroscopy, and identification of neighboring amino acids. The long range noes are then assigned, and three bond coupling constants ate deterrnined. 

A related experiment TOCSY (Total Correlation Spectroscopy) gives similar information and is relatively more sensitive than the REIAY. On the other hand, intensity of cross peak in a NOESY spectrum with a short mixing time is a measure of internuclear distance (less than 4A). It depends on the correlation time and varies as . It is positive for small molecules with short correlation time (o r <<1) and is negative for macromolecules with long correlation time (wr >>l) and goes through zero for molecules with 1 Relaxation effects should be taken into consideration for quantitative interpretation of NOE intensities, however. 

Nuclear Overhauser effect (nOe) The change in intensity in the signal of one nucleus when another nucleus lying spatially close to it is irradiated, with the two nuclei relaxing each other via the dipolar mechanism. Nuclear Overhauser effect correlation spectroscopy (NOESY) A 2D... 

We now want to turn to another experiment which, we must make clear at the start, does not have any relationship in theory to NOE experiments. In fact the theory is so complicated that we shall not say anything about it at all, but just refer you to one of the books in the Appendix. We are including this experiment because of its unique advantages when the spectrum has overlapping multiplets. It is called TOCSY, which stands for Total Correlation SpectroscopY (it has a second, more amusing name HOHAHA, standing for HOmonuclear HArtmann-HAhn), and is of particular use when oligosaccharides or peptides are under study. 

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>. 

Traditional protein NMR spectroscopy of smaller proteins relies of 15N-filtered experiments, due to the relatively low expense of introducing 15N labels into proteins (compared to 13C) and the concomitant ability to use heteronuclear filtering to improve resolution in the H NMR dimension. Jelinek et al. were the first to demonstrate the ability to transfer this approach to peptides on TantaGel.80 They also showed the ability to detect pronounced peptide structure through the appearance of strong NOE correlations in 3H NOESY HRMAS spectra as shown in Fig. 8. This had important implications for the search of biological activity in peptides attached to supports, as the structure on the support may be different or more pronounced than in solution, if present at all in solution in peptides of this small size. 

The structures of the compounds were elucidated by a combination of NMR techniques (lH-, 13C-, and 13C-DEPT NMR) and chemical transformation, enzymatic degradation, and as well as mass spectrometry, which gives information on the saccharide sequence. A more recent approach consists of an extensive use of high-resolution 2D NMR techniques, such as homonuclear and heteronuclear correlated spectroscopy (DQF-COSY, HOHAHA, HSQC, HMBC) and NOE spectroscopy (NOESY, ROESY), which now play the most important role in the structural elucidation of intact glycosides. These techniques are very sensitive and non destructive and allow easy recovery of the intact compounds for subsequent biological testing. 

H is particularly important in NMR experiments because of its high sensitivity and natural abundance. For macromolecules, 1H NMR spectra can become quite complicated. Even a small protein has hundreds of 1H atoms, typically resulting in a one-dimensional NMR spectrum too complex for analysis. Structural analysis of proteins became possible with the advent of two-dimensional NMR techniques (Fig. 3). These methods allow measurement of distance-dependent coupling of nuclear spins in nearby atoms through space (the nuclear Overhauser effect (NOE), in a method dubbed NOESY) or the coupling of nuclear spins in atoms connected by covalent bonds (total correlation spectroscopy, or TOCSY). 

Homonuclear correlation spectroscopy (COSY) experiments (see Chapter 9) substantiate the theoretical predictions, based on molecular orbital calculation, of the pattern of spin delocalization in the 3e orbitals of low-spin Fe(III) complexes of unsymmetrically substituted tetraphenylporphyrins [46]. Furthermore, the correlations observed show that this n electron spin density distribution is differently modified by the electronic properties of a mono-orf/io-substituted derivative, depending on the distribution of the electronic effect over both sets of pyrrole rings or only over the immediately adjacent pyrrole rings [46]. No NOESY cross peaks are detectable, consistently with expectations of small NOEs for relatively small molecules and effective paramagnetic relaxation [47]. 

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>. 

We have investigated peptides whose structures were known beforehand from NMR or x-ray spectroscopy and related these structures to 2D-IR spectroscopy. Ultimately, one would like to deduce the structure of an unknown sample from a 2D-IR spectrum. In the case of 2D NMR spectroscopy, two different phenomena are actually needed to determine peptide structures. Essentially, correlation spectroscopy (COSY) is utilized in a first step to assign protons that are adjacent in the chemical structure of the peptide so that J coupling gives rise to cross peaks in these 2D spectra. However, this through-bond effect cannot be directly related to the three-dimensional structure of the sample, since that would require quantum chemistry calculations, which presently cannot be performed with sufficient accuracy. The nuclear Overhauser effect (NOE), which is an incoherent population transfer process and has a simple distance dependence, is used as an additional piece of information in order to measure the distance in... 

All of the protons in each of 12 thermo- and photochromic BIPS were assigned through a combination of homonuclear decoupling experiments and correlation spectroscopy. The relative stereochemistry of the gem-dimethyl groups could be assigned on the basis of Nuclear Overhauser Effect (NOE) experiments.131... 

The cis stereochemistry adopted by lactam 9 in the course of synthesis was elucidated by H NMR, H- H correlation spectroscopy (COSY), and nuclear Overhauser effect (NOE) experiments taking into account the signals for the hydroxyethyl and benzyl fragments <2002OL2637>. 

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