Dipolar Couplings and Distance Information

4 Dipolar Couplings and Distance Information. - The nuclear Overhauser effect (NOE) arises from dipolar interactions between magnetic moments associated with nuclear spins and it has become a powerful tool to extract relevant pieces of structural information about small molecules, as well as in molecules of biological interest. As a consequence, accurate NOE measurement is a very crucial issue. Walker et presented a comparison between direct and a new inverse HOESY experiment aimed at the detection of heteronuclear NOE between H and which is particularly well suited for symmetric compounds. It transpires that directly detected data are more suitable for quantitative assessment even if they suffer from lower sensitivity, whereas inverse detection is quite appropriate for a quick and quahtative assessment. In the latter experiment, unwanted cross-correlation effects may hide valuable NOE data (cross-relaxation), this drawback can be circumvented by a slight modification of the pulse sequence. 

Kramer and Glaser analysed the transfer efficiency of cross-relaxation compensated (Clean) TOCSY sequences for applications to residual dipolar couplings. Surprisingly most conventional Clean TOCSY sequences are very inefficient for dipolar transfer. It is shown theoretically, that this is a general property of all phase-alternating mixing sequences, i.e., for such sequences the suppression of cross-relaxation excludes dipolar transfer in the spin-diffusion limit. A new family of clean dipolar TOCSY sequences is derived which provides excellent transfer efficiencies for a broad range of offset frequencies. 

Bytchenkoff and Bodenhausen designed a new NMR method for the measurement of the longitudinal relaxation rates of both donor and acceptor N nuclei in Watson-Crick base pairs in N enriched nucleic acids. The length of four hydrogen bonds could be estimated from the longitudinal relaxation rates. 

Almond et investigated how aqueous dynamical simulations of flexible molecules can be compared against NMR data. The methodology compares state-of-the-art NMR residual dipolar coupling, NOESY and relaxation, to molecular dynamics simulations in water over several nanoseconds. In contrast to many previous applications of residual dipolar couplings in structure investigation of biomolecules, the approach described here uses MD simulations to provide a dynamic representation of the molecules. 

The measurement of residual dipolar couplings in weakly aUgned proteins can potentially provide unique information on their structure and dynamics in the solution state. The challenge is to extract the information of interest from the measurements, which normally reflect a convolution of the structural and dynamic properties. Tolman et alP discussed a formalism which allows a first 

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There are three aspects to consider. First, we summarize briefly the underlying computational framework needed and the general strategy used in the structure determination. Second, we cover the use of 2D, 3D, and 4D methods to permit the sequential assignment of peaks to specific amino acids. Finally, we describe the use of nuclear Overhauser enhancements and spin coupling constants to provide restraints on interproton distances and bond angles, and we indicate how dipolar coupling and chemical shifts can sometimes add further information on molecular conformation. 

In the following, we will discuss heteronuclear polarization-transfer techniques in four different contexts. They can be used as a polarization-transfer method to increase the sensitivity of a nucleus and to shorten the recycle delay of an experiment as it is widely used in 1H-13C or 1H-15N cross polarization. Heteronuclear polarization-transfer methods can also be used as the correlation mechanism in a multi-dimensional NMR experiment where, for example, the chemical shifts of two different spins are correlated. The third application is in measuring dipolar coupling constants in order to obtain distance information between selected nuclei as is often done in the REDOR experiment. Finally, heteronuclear polarization transfer also plays a role in measuring dihedral angles by generating heteronuclear double-quantum coherences. 

As mentioned in Sections I.B.2.b and II.A, the dipolar coupling between Li- C may complicate solid state NMR spectra of organolithium compounds and its elimination is often desirable. On the other hand, dipolar coupling constants are related to atomic distances and their determination can yield important structural information. It is therefore of general interest that the REDOR technique, briefly described in Section I.B.2.b, provides a means to determine these parameters. 

Relaxation measurements provide a wealth of information both on the extent of the interaction between the resonating nuclei and the unpaired electrons, and on the time dependence of the parameters associated with the interaction. Whereas the dipolar coupling depends on the electron-nucleus distance, and therefore contains structural information, the contact contribution is related to the unpaired spin density on the various resonating nuclei and therefore to the topology (through chemical bonds) and the overall electronic structure of the molecule. The time-dependent phenomena associated with electron-nucleus interactions are related to the molecular system, and to the lifetimes of different chemical situations, for the resonating nucleus. Obtaining either structural or dynamic information, however, is only possible if an in-depth analysis of a series of experimental results provides sufficient data to characterize the system within the theoretical framework discussed in this chapter. 

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