NOESY chain conformation

NOESY has also been used to elucidate the chain conformation of poly(styrene-a/ -MMA).220,221 2D INADEQUATE has been applied to studies of monomer sequence distribution in ethylene-propylene copolymer.223 Additivity rules for the 13C chemical shifts of ethylene-propylene copolymer were devised for configurational sequences as well as substituent effects.226... 

For PPI dendrimers, multidimensional NMR experiments based on the nuclear Overhauser effect (NOE) such as NOESY-HSQG 3D-NMR and NOESY 2D-NMR techniques have been used to study conformations of the dendrimer and interactions with solvents of different polarity. For these amino-terminated dendrimers, it was concluded that folded chain conformations are predominant in nonpolar solvents such as benzene, while a more extended chain conformation is obtained in more polar solvents such as chloroform. As shown in Figure 29, 2D-NOESY spectroscopy can be used to determine the nuclear Overhauser interactions in the dendrimer structure. In chloroform, the structure becomes more extended as seen by the clear NOE cross-peaks between the solvent(s) and the dendritic structure, whereas in a less good solvent (e.g., benzene), such NOE peaks are not seen, suggesting a more compact structure. 

Homonuclear correlation via the nuclear Overhauser effect (NOESY). The NOESY experiment correlates peaks by means of the nuclear Overhauser enhancement and so identifies pairs of nuclei which are sufficiently close together in space to relax by their dipole-dipole interaction. This technique is not so applicable in determining stereochemical assignments as those described previously, but may be extremely useful in determining the chain conformation as demonstrated by Mirau et al. in a study of the alternating copolymer of styrene and methyl methacrylate [45] (see chapter 4). 

Combining 2D-NOESY and 2D-ROESY NMR experiments with molecular modelling protocols, Kuhn and Kunz32 have been able to study the saccharide-induced peptide conformational behaviour of the recognition region of Ll-Cadherin. The detailed conformational analysis of this key biomolecule not only proves that the saccharide side chain exerts a marked influence on the conformation of the peptide chain, but also that the size and type of the saccharide indeed strongly affects the conformation of the main chain. 

Based on the backbone-rigidification strategy, oligomers with sufficiently long (> 7 subunits) backbones should adopt helical conformations in which one end of the molecule lies above the other. Extensive NOESY studies on the symmetrical nonamer 4 confirmed this expectation [50]. In addition to the presence of numerous well-resolved amide-side chain NOEs, the NOESY spectrum of 4 also revealed an end-to-end NOE cross peak between the end methyl (Me) protons and aromatic proton b 1 (Fig. 7). Due to the symmetrical... 

Variable-temperature NOESY experiments performed on 4 showed that the Me- -bl NOE disappeared much more rapidly than the amide-side chain NOEs (Fig. 9), suggesting that the hydrogen bond rigidified backbone was quite resilient toward heating. Most likely, this molecule breathes and extends like a spring but maintains its overall helical conformation. 

We recently characterized undecamer 6 using NOESY (Fig. 10), which revealed numerous amide-side chain NOEs that were fully consistent with a three-center hydrogen bond rigidified backbone [52]. Three sets of long-range NOEs (indicated in Fig. 10a), which were not detected in the NOESY spectrum of a hexamer that was about half of 6, suggest that 6 did indeed adopt a helical conformation. 

Fig. 12 a End-to-end NOEs as revealed by the NOESY spectrum of 7. The helical conformation of 7 is consistent with the NOEs (indicated by purple arrows). All long side chains are replaced with methyl groups for clarity... 

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