Selective relaxation rates

Thus, identification of all pairwise, interproton relaxation-contribution terms, py (in s ), for a molecule by factorization from the experimentally measured / , values can provide a unique method for calculating interproton distances, which are readily related to molecular structure and conformation. When the concept of pairwise additivity of the relaxation contributions seems to break down, as with a complex molecule having many interconnecting, relaxation pathways, there are reliable separation techniques, such as deuterium substitution in key positions, and a combination of nonselective and selective relaxation-rates, that may be used to distinguish between pairwise, dipolar interactions. Moreover, with the development of the Fourier-transform technique, and the availability of highly sophisticated, n.m.r. spectrometers, it has become possible to measure, routinely, nonselective and selective relaxation-rates of any resonance that can be clearly resolved in a n.m.r. spectrum. 

According to these equations, the effect of selectively perturbing the spin states of spins i and j is to isolate the cross-relaxation paths common to these two spins. Combining Eqs. 15 and 19, the individual cross-relaxation terms are readily determined from single-selective and double-selective relaxation-rate measurements, that is. 

It is apparent from the foregoing discussion that several precautions are necessary in order to obtain accurate measurements of nonselective and selective relaxation-rates. Under these conditions, and with the availability of the modern Fourier-transform instrumentation, it is now possible to measure relaxation rates with an accuracy of 1-3%. The reward is great accurate information about the structure and conformation of molecules in the liquid phase, as will be seen in the following section. 

The second separation method involves n.O.e. experiments in combination with non-selective relaxation-rate measurements. One example concerns the orientation of the anomeric hydroxyl group of molecule 2 in Me2SO solution. By measuring nonselective spin-lattice relaxation-rat s and n.0.e. values for OH-1, H-1, H-2, H-3, and H-4, and solving the system of Eq. 13, the various py values were calculated. Using these and the correlation time, t, obtained by C relaxation measurements, the various interproton distances were calculated. The distances between the ring protons of 2, as well as the computer-simulated values for the H-l,OH and H-2,OH distances was commensurate with a dihedral angle of 60 30° for the H-l-C-l-OH array, as had also been deduced by the deuterium-substitution method mentioned earlier. 

Single- and double-selective relaxation-rates, together with n.O.e. experiments, have been used to examine the configuration and conformation of asperlin (1) in benzene solution." " Comparing experimental distances for the proton pairs H-4,H-7 and H-5,H-7 with those obtained from molecular models, it was possible to confirm earlier evidence that the oxirane ring is trans, and also to show that, of the two possible diastereoisomeric forms (49a and 49b), the data are more fully compatible with structure 49a, the... 

However, the relaxation contributions obtained from Eq. 22 were not satisfactorily compared with those obtained from specific, deuterium-substitution experiments and single- and double-selective relaxation-rates. Moreover, the errors estimated for the triple-pulse experiments were very much larger than those observed for the other techniques. This point will be discussed next. 

Combinations of non-selective and/or single-selective relaxation-rates, or both, with n.0.e. values may conveniently be performed with reliable results, especially when other methods seem impractical. However, these experiments are time-consuming, as they entail the determination of a rather large number of experimental values. Moreover, the n.O.e. parameters carry their own systematic and random errors, which are magnified in the calculation of interproton distances. The deuterium-substitution method requires specific deuteration at a strategic position, which, in many cases, may be inconvenient or impractical. Also, this technique is valid only when the relaxation rates obtained after deuterium substitution are at least 5% enhanced, relative to the relaxation rates of the unsubstituted compound, and it requires that, for a meaningful experiment, the following condition " be satisfied. 

Stage 1 involves first the determination of the Ri-value of the protons (A) of interest by the two-pulse sequence (10) referred to earlier, in which the perturbing, 180°-pulse is applied in a non-selective fashion to all the proton resonances (we shall refer to this value as the non-selective relaxation rate (ns)). Then the two-pulse sequence is repeated, except that now the 180°-pulse is applied selectively (11), (12) to just the A-resonance, and the recovery back to thermaT equTTibrium of the magnetisation of A is monitored with the usual non-selective 90° pulse this gives a new relaxation rate constant, the single-selective relaxation rate (R ()C) where Vindicates the nucleus which has been subjected to the single-selective 180° pulse). 

The spectra shown in figures 2 and 3 illustrate the determination of the non-selective and single-selective relaxation rates for the anomeric proton of methyl e-D-glucopyranoside, and the resultant data, along with that of the a-anomer and the two trideuteriomethyl glucosides is given in Table I. It is... 

Let us now see how this explicit relationship, in conjunction with the initial non-selective relaxation rates, can be used to determine the contribution which the methoxyl protons of a methyl glycoside make to the relaxation of the anomeric proton H-l. 

Referring back to the Ri-values given in Table I it is a trivial matter to calculate the relaxation contributions between the methoxyl protons and H-l for the two methyl D-glucopyrano-sides and these values are listed below in Table II. Not surprisingly, there is excellent agreement between the values calculated from the non-selective and single-selective relaxation rates. 

Encouraged by the above experiments, it was decided to extend this selective deuteration approach to a disaccharide and for reasons of synthetic convenience, p-D-glucopyranosyl-(l 6i)-D-galactopyranose and its 6,6-di-deuterio analog were synthesised (see Flow Sheet I). The non-selective relaxation rates for the... 

We measured the selective relaxation rates of some protons nuclei of 22 and by extrapolation of the normalized affinity indices for these protons we were able to highlight the nuclei mainly involved in the interaction between receptor 22 and ChT, which is at the basis of the inhibition. Unlike what we expected, most of the interaction affects protons which belong to the resorcarene core rather than to the dipeptide side chain, thus suggesting that the hydrophobic portion of the macrocycle mainly stabilizes the [22 ChT] complex, causing the loss of the proteolytic ChT activity. 

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