Equilibria conformational

A number of issues need to be addressed before this method will become a routine tool applicable to problems as the conformational equilibrium of protein kinase. E.g. the accuracy of the force field, especially the combination of Poisson-Boltzmann forces and molecular mechanics force field, remains to be assessed. The energy surface for the opening of the two kinase domains in Pig. 2 indicates that intramolecular noncovalent energies are overestimated compared to the interaction with solvent. 

Theoretical work by the groups directed by Sustmann and, very recently, Mattay attributes the preference for the formation of endo cycloadduct in solution to the polarity of the solvent Their calculations indicate that in the gas phase the exo transition state has a lower energy than the endo counterpart and it is only upon introduction of the solvent that this situation reverses, due to the difference in polarity of both transition states (Figure 1.2). Mattay" stresses the importance of the dienophile transoid-dsoid conformational equilibrium in determining the endo-exo selectivity. The transoid conformation is favoured in solution and is shown to lead to endo product, whereas the cisoid conformation, that is favoured in the gas phase, produces the exo adduct This view is in conflict with ab initio calculations by Houk, indicating an enhanced secondary orbital interaction in the cisoid endo transition state . 

The last example is somewhat more complicated since four isomers (two tautomers and two conformations) are present at equilibrium (Figure 9) (78BSB189). The experimental value (3.73 D, Table 3) establishes the predominance of the 3-azido tautomer but does not allow the determination of the conformational equilibrium other methods (Section 4.04.2.3.4(v)) are necessary to establish definitely the Z conformation (43b). 

In cyclic systems such as 1, the dominant conformation is the one with the maximum anomeric effect. In the case of 1, only conformation lA provides the preferred antiperiplanar geometry for both oxygens. Antiperiplanar relationships are indicated by including lone pairs in the oxygen orbitals. Other effects, such as torsional strain and nonbonded repulsion, contribute to the conformational equilibrium, of course. Normally, a value of about 1.5 kcal/mol is assigned to the stabilization due to an optimum anomeric interaction in an acetal. 

The Coleman-Fox two state model describes the situation where there is restricted rotation about the bond to the preceding unit (Scheme 4.3). If this is slow with respect to the rate of addition, then at least two conformations of the propagating radical need to be considered each of which may react independently with monomer. The rale constants associated with the conformational equilibrium and two values of Pirn) are required to characterize the process. 

Bcrnoullian statistics do not provide a satisfactory description of the tacticity. 6 This finding is supported by other work.28" 38 First order Markov statistics provide an adequate fit of the data. Possible explanations include (a) penpenultimale unit effects are important and/or (b) conformational equilibrium is slow (Section 4.2.1). At this stage, the experimental data do not allow these possibilities to be distinguished. 

Hall et al.1 s estimated the conformational equilibrium for the structural units in the polymer of 2 using the numerical parameters determined for carbohydrates16. For a frans-l,3-tetrahydropyranoside, conformer 8 is calculated to be more stable than 7 by 9.2 kJmol-1 and would therefore occur almost exclusively (ca. 98%) at equilibrium. For a m-1,3-tetrahydropyranoside unit, the anomeric effect favors con-former 9, but its severe syn-axial interaction between alkoxy and alkyl groups would highly favor 10 (ca. 99%). 

Most of these results have been obtained in methanol but some of them can be extrapolated to other solvents, if the following solvent effects are considered. Bromine bridging has been shown to be hardly solvent-dependent.2 Therefore, the selectivities related to this feature of bromination intermediates do not significantly depend on the solvent. When the intermediates are carbocations, the stereoselectivity can vary (ref. 23) widely with the solvent (ref. 24), insofar as the conformational equilibrium of these cations is solvent-dependent. Nevertheless, this equilibration can be locked in a nucleophilic solvent when it nucleophilically assists the formation of the intermediate. Therefore, as exemplified in methylstyrene bromination, a carbocation can react 100 % stereoselectivity. 

In six-membered rings containing heteroatoms, the basic principles are the same that is, there are chair, twist, and boat forms, axial and equatorial groups, and so on. The conformational equilibrium for tetrahydropyridines, for example has been studied. In certain compounds, a number of new factors enter the picture. We deal with only two of these. ... 

For example, the rigid, planar flavone 84 is completely tasteless. Phyllodul-cin (77) and the flavanones 79 and 80, on the other hand, can exist in a conformational equilibrium between a planar form (with the B-ring in the quasiequatorial disposition) and a bent form (with the B-ring assuming a quasiaxial orientation). Fig. 23,i presents the best binding to the receptor site. 

Fig. 24 Conformational equilibrium for 48 caused by chirality transfer to the sulfonylated W-atom...

Reactive intermediates in solution and in the gas phase tend to be indiscriminant and ineffective for synthetic applications, which require highly selective processes. As reaction rates are often limited by bimolecular diffusion and conformational motion, it is not surprising that most strategies to control and exploit their reactivity are based on structural modihcations that influence their conformational equilibrium, or by taking advantage of the microenvironment where their formation and reactions take place, including molecular crystals. ... 

Finally, it should be mentioned that all our arguments and examples have centered on the syn conformer of the o-methylbenzoy1 group. In small molecules the syn-anti conformational equilibrium is known to play an important role in the photochemistry of the... 

Caminati, W., A. C. Fantoni, B. Velino, K. Siam, L. Schafer, J. D. Ewbank, and C. Van Alsenoy. 1987a. Conformational Equilibrium and Internal Hydrogen Bonding in 2-Methylallyl Alcohol Detection of a Second Conformer by Microwave Spectroscopy on the Basis of Ab Initio Structure Calculations. J. Mol. Spectrosc. 124, 72-81. 

The temperature measurements in range from —40 to 23 °C revealed the presence of conformational equilibrium between conformers of the opposite helicity (M- and P-helix). The barrier of 13 kcal/mol of the chemical exchange was estimated. It was shown that peripheral stereocenters control the absolute sense of helicity in the foldamers studied.103... 

On the basis of the splitting of several JH signals in the 20- and 40-membered U02 complexes, [11], [12] being derivatives of (R)-binol, Amato et al.27 have suggested the presence of a conformational equilibrium. For the 20-membered complex, the rate constant at 300 K was... 

On the basis of X-ray analysis of 1,2-oxaphosphole derivatives authors suggested [68] that these compounds have planar symmetry or that there is a process of rapid conformational equilibrium. 

French workers have studied the 1H- and 13C-NMR parameters of disubstituted selenophenes.37 38 The proton chemical shifts are discussed in terms of magnetic anisotropy and electric field effects of the substituents in order to study the conformational equilibrium of the carbonyl group. The relationship between the H- and 13C-chemical shifts and 7t-electron distribution calculated by the PPP method are examined. Shifts and coupling constants are discussed in additivity terms. 

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