Conformational exchange

Since there is only a small energy difference between the different conformational states depending upon the presence or absence of a Pro, Gly or N-alkylated amino acid residue, and upon the chirality of the constituent amino acid residues and also to a lesser extent upon the side-chain functionalities, it is not possible to unambiguously predict the conformation of a cyclic pentapeptide. These molecules have often been studied in different solvents and solvent effects were neglected, and/or the methodology to handle such conformational equilibrium was not available. It is only recently that modem NMR techniques and computational procedures have become available to treat this complex problem of fast exchanging conformational equilibria. 36,269,270 ... 

Diarylethene switches are present in two, rapidly exchanging conformations (P and M helicity), which upon photochemical ring-closure lead to the RR or SS enantiomers in equal amounts. The authors showed that aggregation of a chiral diarylethene switch in the open form 283 leads to selection of only one of the helical forms of 283 in the gel state. Subsequent photochemical ring-closure of 283 to 284 in the gel state proceeds with 96% diastereoisomeric excess and a photosta-tionary state (PSS) of 40%, whereas in solution, no stereoselection is observed. 

Adsorption of proteins onto surfaces involves a complex interplay of reversibility, exchange, conformational change, irreversible attachment, and denaturation. Several of these processes may be followed by measurement of the circular dichroism of adsorbed species and of desorbed material. The profile of chromatographically adsorbed material also contains, in principle, the details of the complex kinetics. Some aspects of each of these processes are examined. 

The most common observable mechanisms for averaging the environments of protons, or of groups of equivalent protons, that can be observed on the NMR time-scale are proton exchange, conformational changes, and rotation about partial doublebonds. An example of each follows ... 

Polyelectrolyte, Carbox5methylcellulose, Pectin, Carrageenan, Alginate, Cationic starch, Galactomannan, Lignosulphonate, Ion exchange. Conformational transition. Physical gelation. Electrostatic complex, Chitosan... 

Scheme la, X = CH3). Well-resolved spectra of propagating radicals of tert-butyl methacrylate (rBMA) have been detected in such polymerization systems at various temperatures as shown in Figure 1,16-line spectra were clearly observed. The spectroscopic feature of the spectra showed a clear temperature dependence which can be interpreted by a hindered rotation model of two stable conformations. The intensity of the inner 8 lines increased with increasing temperature, indicating that there are two exchangeable conformations whose existence have been shown by elucidation of ESR spectra of methacrylates. 

Wallace, K. J., Belcher, W. J., Turner, D. R., Syed, K. F. and Steed, J. W., Slow anion exchange, conformational equilibria and fluorescent sensing in Venus flytrap aminopyridinium-based anion hosts, . Am. Chem. Soc., 2003,125,9699-9715. 

Judeinstein et al have conducted direct measurement of through-space NMR interactions that provide definitive evidence for spatial proximity of different species. Dipole-dipole interactions can be measured in principle between any NMR active nuclei with heteronuclear correlation experiments in the liquid or solid state." The dipole-dipole interactions decay quickly with the internuclear distances (r ), and are difficult to evaluate for long-range distances and even more difficult when exchange, conformation, or motion phenomena are present. However, the measurement of the nuclear Overhauser method" based on the dipole-dipole-induced crossrelaxation, was proposed to successfully measure intermolecular interactions" and the formation of ion pairs." " In agreement with recent studies, the pulsed field gradient enhanced inverse HOESY (heteronuclear Overhauser enhancement spectroscopy) sequence is usually preferred because it is more sensitive for isotope pairs H- Li and also improves the digital resolution in the H crowded spectrum." ... 

Backbone generation is the first step in building a three-dimensional model of the protein. First, it is necessary to find structurally conserved regions (SCR) in the backbone. Next, place them in space with an orientation and conformation best matching those of the template. Single amino acid exchanges are assumed not to affect the tertiary structure. This often results in having sections of the model compound that are unconnected. 

The most characteristic coupling constant in indazoles is the cross-ring Vs, present both in indazoles and in isoindazoles unsubstituted in positions 3 and 7. 2-Methyl isomers show an additional Vmc.h coupling which can serve to identify an isoindazole unsubstituted in position 3. In 3-azidoindazole, as in 3-azidopyrazole (56), the prototropic exchange is slowed down sufficiently to allow the measurement of a zig-zag /i,4 coupling constant. The deshielding effects observed in A-acetyl derivatives, e.g. 1-acetyl (60) on H-7 and 2-acetyl (61) on H-3, are related to a preferred E conformation (Section 4.04.1.4.3). 

Modification of Table 5-10 to make the total-exchange areas conform to the gray-plus-clear gas model is straightforward, following the instructions presented above. The results are given in Table 5-11. 

As the coiled plate spirals outward, the plate thickness increases from a minimum of 2 mm to a maximum (as required by pressure) up to 10 mm. This means relatively thick material separates the two fluids compared to tubing of conventional exchangers. Pressure vessel code conformance is a common request. 

AE Garcia, G Hummer. Conformational dynamics of cytochrome c CoiTelation to hydrogen exchange. Proteins 36 175-191, 1999. 

Energy differences between conformations of substituted cyclohexanes can be measured by several physical methods, as can the kinetics of the ring inversion processes. NMR spectroscopy has been especially valuable for both thermodynamic and kinetic studies. In NMR terminology, the transformation of an equatorial substituent to axial and vice versa is called a site exchange process. Depending on the rate of the process, the difference between the chemical shifts of the nucleus at the two sites, and the field strength... 

For substituted cyclohexanes, the slow-exchange condition is met at temperatures below about —50 C. Table 3.5 presents data for the half-life for conformational equilibration of cyclohexyl chloride as a function of temperature. From these data, it can be seen that conformationally pure solutions of equatorial cyclohexyl chloride could be maintained at low temperature. This has been accomplished experimentally. Crystallization of cyclohexyl chloride at low temperature affords crystals containing only the... 

Since the conformational inversion of 2c-methylcyclohexanone is the key step in this sequence, the corresponding conformationally more stable system, i.e., cw-2-methyl-4-t-butylcyclohexanone (14), should fail to incorporate any deuterium. This was actually shown to be the case. Treatment of this ketone under identical conditions for d exchange did not show any d incorporation. This evidence also rules out the likelihood of any d incorporation via acid- or base-catalyzed enolization. 

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