Proximity through space

NUCLEAR OVERHAUSER EFFECT, DIFFERENCE SPECTROMETRY, H H PROXIMITY THROUGH SPACE 1 73... 

There are still two remaining tasks assignment of stereochemistry of the C-2, C-3-double bond and assignment of the C-8 and C-9 methyl groups. NOE difference spectrometry is described in Section 3.16. It is a 1-D experiment that reveals H— H proximity through space because of enhancement by the nuclear Over-hauser effect. The difference spectrum is obtained by subtracting a standard H spectrum from the NOE spectrum this leaves only the enhanced peak(s). 

Nuclear Overhauser Effect Difference Spectrometry, H H Proximity Through Space 189... 

NOE difference spectrometry is described in Section 4.20. It is a 1-D experiment that determines JH—JH proximity through space. The difference spectrum is obtained by subtracting a standard H spec-... 

As with the COSY experiment, the sequence starts with a pulse followed by an evolution period, but now the mechanism that couples the two spins (which must be in close proximity, typically <6 A) is the Nuclear Overhauser Effect (NOE). The second pulse converts magnetization into population disturbances, and cross-relaxation is allowed during the mixing time. Finally, the third pulse transfers the spins back to the x-y-plane, where detection takes place. The spectrum will resemble a COSY spectrum, but the off-diagonal peaks now indicate through-space rather than through-bond interactions. 

These experiments provide identification of the through-bond spin coupling network as well as through-space proximity between spins. Examples of the application of these techniques have demonstrated the efficiency of these techniques in establishing the assignment, sequence and linkage site information for oligo- and poly-saccharides [59-60, 62-65], and for saponins [29]. 

Significant through-space scalar couplings have been observed only in rare cases and in very close spatial proximity and usually 19F is involved in such couplings102-105, e.g., in the following fluorinated polycyclic aromatic systems ... 

Recently,94,166,167 it was reported that the through-space TSJ(F, F) coupling between proximate F atoms can have a substantial contribution from the PSO term. It is important to stress that comments made above about interactions... 

Although through-space pathways for J(F, C) couplings such as, for instance, the proximate -electronic systems in cyclophenes [19] are known,245 most commonly TSJ(F, C) couplings correspond to configurations where they... 

Enolization of cationic ketones is accelerated by electrostatic stabilization of the enolate anion. Rate constants for water-, acetate-, and hydroxide ion-catalysed enolization of 2-acetyl- 1-methylpyridinium ion (94) have been measured13811 and compared with a 2-acetylthiazolium ion (95), a simple analogue of 2-acetylthiamine pyrophosphate.13811 For (94), qh = 1.9 x 102 M-1 s 1, about 1.1 x 106 times that for a typical methyl ketone such as acetone. Thermodynamically, it is >108 times more acidic (pAa values of 11.1 vs 19.3). These increases in kinetic and thermodynamic acidity are derived from through-bond and through-space effects, and the implications for enzymatic catalytic sites with proximal, protonatable nitrogen are discussed. The results for (94) suggest a pAa value of 8.8 for (95), a value that cannot be measured directly due to competing hydrolysis. 

Fig. 1. Depiction of the concept of electrochemical recognition the binding of a guest (G) in close proximity to a redox-active center electrochemically detectable (a) through space interactions and (b) through various bond linkages.

The through-space distances involved in H H proximity determinations are quite small, and the effect decreases as the inverse of the sixth power of the distance, through space, between the protons. The usual observable enhancement is less than 20%. To increase the sensitivity, we use the NOE difference experiment, in which a conventional H spectrum is computer sub-... 

In Chapter 3 (Section 3.16), there is a description of the nuclear Overhauser effect difference experiment, an experiment that provides information about H— H through-space proximity. Review of this section is helpful before proceeding here. The ROESY experiment, rotating-frame Overhauser effect spectroscopy, is a useful 2-D analogue of the nuclear Overhauser effect difference experiment. This experiment is useful for molecules of all sizes whereas the related experiment, NOESY (nuclear Overhauser effect spectroscopy), is not very useful with small molecules. NOESY is used primarily with biological macromolecules. Both NOESY and ROESY experiments correlate protons that are close to each other in space, typically 4.5 A or less. 

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