Proton distances determined

Figure 15 The model molecule used to demonstrate the possibilities of HOESY experiments in terms of carbon-proton distances and reorientational anisotropy. To a first approximation, the molecule is devoid of internal motions and its symmetry determines the principal axis of the rotation-diffusion tensor. Note that H, H,., H,-, H,/ are non-equivalent. The arrows indicate remote correlations.

An interesting question then arises as to why the dynamics of proton transfer for the benzophenone-i V, /V-dimethylaniline contact radical IP falls within the nonadiabatic regime while that for the napthol photoacids-carboxylic base pairs in water falls in the adiabatic regime given that both systems are intermolecular. For the benzophenone-A, A-dimethylaniline contact radical IP, the presumed structure of the complex is that of a 7t-stacked system that constrains the distance between the two heavy atoms involved in the proton transfer, C and O, to a distance of 3.3A (Scheme 2.10) [20]. Conversely, for the napthol photoacids-carboxylic base pairs no such constraints are imposed so that there can be close approach of the two heavy atoms. The distance associated with the crossover between nonadiabatic and adiabatic proton transfer has yet to be clearly defined and will be system specific. However, from model calculations, distances in excess of 2.5 A appear to lead to the realm of nonadiabatic proton transfer. Thus, a factor determining whether a bimolecular proton-transfer process falls within the adiabatic or nonadiabatic regimes lies in the rate expression Eq. (6) where 4>(R), the distribution function for molecular species with distance, and k(R), the rate constant as a function of distance, determine the mode of transfer. 

The calculation of IV (succinic) was carried out twice, for / (C = C ) = 1.3 A and / (Cju - Cjj) = 1.54 A. If the correlation were determined by the electrostatic interaction alone, we should have weakened the interaction upon increasing the proton-proton distance. In Table 4.4, we see that by increasing the C - C distance (keeping all other parameters fixed) we actually increase the value of IV. This is clearly due to the relatively large effect of the indirect positive correlation in the equilibrated system. Unfortunately, the relative contribution of the direct and indirect correlations cannot be determined from the experimental data. The computed values of IV = kgT In y(l, 1) are shown in brackets in Table 4.4. It is seen that a large negative contribution to IV(1,1) is due to the indirect cooperativity. 

Because of the dependence of the inner sphere relaxivity on l/r, the Gd-water proton distance is extremely important in determining the efficacy of a CA. In Fig. 8 the experimental profile of [GdDTPA(H20)] is shown and also the best-fit curve obtained with a th value of 3.1 A, compared with two calculated profiles corresponding to th values of 2.95 (upper curve) and 3.25 A. A variation of this parameter of only 0.15 A changes the relaxivity about 16% at low fields. Estimates from X-ray data of the Gd-0 distance are affected by some errors as the tilt angle of the water molecule in solution is not defined with precision. 

Until now, the determination of three-dimensional structures of oligosaccharides in solution was based primarily on proton-proton distance information obtained from n.O.e. data. Here, we discuss the application of three-bond proton-carbon coupling constants. 

The basis for the determination of solution conformation from NMR data lies in the determination of cross relaxation rates between pairs of protons from cross peak intensities in two-dimensional nuclear Overhauser effect (NOE) experiments. In the event that pairs of protons may be assumed to be rigidly fixed in an isotopically tumbling sphere, a simple inverse sixth power relationship between interproton distances and cross relaxation rates permits the accurate determination of distances. Determination of a sufficient number of interproton distance constraints can lead to the unambiguous determination of solution conformation, as illustrated in the early work of Kuntz, et al. (25). While distance geometry algorithms remain the basis of much structural work done today (1-4), other approaches exist. For instance, those we intend to apply here represent NMR constraints as pseudoenergies for use in molecular dynamics or molecular mechanics programs (5-9). 

The hyperfine shifts of groups bound to the donor atom are largely dominated by the contact interaction, even if pseudocontact shift contributions are sizable and any quantitative use of the shifts should rely on the separated contributions. Longitudinal nuclear relaxation times can be used, and have been used in the case of cobalt substitute stellacyanin, to determine metal-proton distances [101]. The contribution of Curie relaxation, estimated from the field dependence of the linewidths, can be used both for assignment and to determine structural constrains [101]. 

The preferred conformation of related 2-substituted /ra j--l,3-dithia-5,6-benzocycloheptene 1-oxides 43 depends on the substitution pattern. Compounds 43b-f (R = phenyl, methyl, ethyl, isopropyl) exist in CDC13 at — 60 °C as an equilibrium of chair and boat conformations with the substituents in the equatorial position. Unsubstituted 43a (R = H) possesses a boat form with an axial sulfinyl group whereas, for the butyl derivative the conformational equilibrium is completely shifted to the boat structure. The proton-proton distances for the chair conformer of 2-phenyl-l,3-dithia-5,6-benzocycloheptene 1-oxide 43b were determined by 2D NOESY experiments in CD2CI2 and CS2-CDCI3. It has been shown that solvent effects influence the thermodynamic parameters of the conformational equilibrium <2001JGU1266>. 

As we have seen above, a large number of parameters (proton exchange rate, kex = l/rm rotational correlation time,. electronic relaxation times, 1/TI 2(, Gd - proton distance, rG H hydration number, q) influence the inner sphere proton relaxivity. If the proton exchange is very slow (Tlm < rm), it will be the only limiting factor (Eq. (5)). If it is fast (rm Tlm), proton relaxivity will be determined by the relaxation rate of the coordinated protons, Tlm. which also depends on the rate of proton exchange, as well as on rotation and electronic relaxation. The optimal relationship is ... 

Based on this equation, the NOE gives a measure of the distance between two nuclei, typically up to a maximum observable distance of about 5 A. The distances determined for proton pairs in a peptide can be used as restraints in simulated annealing approaches for the calculation of the 3D structure of the peptide (38-40). 

If the metal to proton distance, r, is known it is then possible to determine the correlation time, rc. An alternative method measures the nuclear TJm enhancement at several frequencies then the geometric factor and the correlation time can be calculated through a least squares analysis59. It is usually assumed that rc is determined by the electron spin-lattice relaxation time. 

Figure 4.46. Detecting Short Proton-Proton Distances. A NOESY spectrum for a 55 amino acid domain from a protein having a role in RNA splicing. Each off-diagonal peak corresponds to a short proton-proton separation. This spectrum reveals hundreds of such short proton-proton distances, which can be used to determine the three-dimensional structure of this domain. [Courtesy of Barbara Amann and Wesley McDermott.]...

A—H Distances in Hydrogen Bonded Crystals. There are a few scattered data for A—H B bonds where either A or B is not oxygen. Most of these cases were studied by proton magnetic resonance and, in some, proton-proton distances were determined rather than A—H distances. Table 9-IV shows the data available. 

Clearly though, even a purely qualitative evaluation of the geometric influences of the anomeric and exo-anomeric effects based on a new independent measurement tool, has some considerable relevance and further studies on this topic are being actively pursued at this time. And to leave the more sceptical readers of this article with some positive food-for-thought, we summarise below in Table V the interproton distances, determined (22.) by proton relaxation measurement, for an organic molecule, the bicycloheptene portion of XII which is, according to all presently available criteria, tumbling isotropically. 

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