Conformation population effects

Cifra, P. and Bleha, T. Conformer populations and the excluded volume effect in lattice simulations of flexible chains in solutions, Polymer, 34 (1993). 3716-3722... 

The acid-catalyzed ester hydrolysis provides a good target for MM treatments. DeTar first used hydrocarbon models in which an ester was approximated by an isoalkane (74) and the intermediate (75) by a neoalkane (76). He assumed that if the rate of reaction truly is not influenced by polar effects but is governed only by steric effects of R, as has been generally postulated, the rate must be proportional to the energy difference (AAH ) between 74 and 76. The AAH f is mainly determined by the van der Waals strain in these branched alkanes. Nonsteric group increment terms were carefully adjusted, and statistical mechanical corrections for conformer populations... 

Inductive effects on dipole moments and the effects of intervening atoms on electrostatic interaction energies are represented by polarizability centers In conjunction with bond centered dipoles. Solvation energies are estimated by means of a continuum dlpole-quadrupole electrostatic model. Calculated energies of a number of conformations of meso and racemic 2,4-dichloropentane and the iso, syndio, and hetero forms of 2,4,6-triehloroheptane give satisfactory representations of isomer and conformer populations. Electrostatic effects are found to be quite important. 

It is obvious that independently of the rate of exchange the NMR spectrum of a system subject to a dynamic equilibrium depends on the relative concentrations of the components present. These may be expressed as mole fractions or, in the case of intramolecular exchange, as conformer populations. Sometimes the populations are governed by symmetry effects alone and are independent of the experimental conditions. This is always the case for mutual exchange when the process does not alter the chemical identity of a molecule. Examples of such exchange may be drawn from rotations of the t-butyl group in (CH3)3C-C(R1)(R2)(R3), and those about the CO-N bond in N,N-dimethyl-substituted amides (CH3)2N-C(=0)R. Other examples include ring inversions such as those in 1,2-ds-dimethylcyclohexane, 1,3-trans-... 

The PCM/DFT model failed to predict the intrinsic rotation (i.e. the specific rotation extrapolated to infinite dilution) of (R)-3-methylcyclopentanone dissolved in carbon tetrachloride, methanol and acetonitrile [68], This molecule has been investigated because it exists in both an equatorial and an axial form, allowing researchers to investigate the interplay of solvent and conformational effects. The conformer populations used in the Boltzmann averaging were derived from IR absorption and VCD spectra. The deviation of the calculated optical rotation from experiment was found actually to be larger when IEF-PCM was used to account for direct solvent effects (and geometry relaxation) on the optical rotation than when the gas-phase values were used. 

Dipole-dipole interactions have been used to assess the conformational populations of 2-haloketones (Eliel et al., 1965). With respect to SS, however, there are few applications in which these and related effects are considered. It is interesting that dipole induction and London dispersion effects were used some thirty years ago to account for the high endo over exo preference in the Diels-Alder reaction (Wassermann, 1965). Although effects are small for any pair of atoms, there are many closely packed atoms in a Diels-Alder transition state. At a carbon-carbon distance of 2-0 a between the atoms to be bonded, the energy favoring endo addition is 2-7 for dipole induction and 3-4 kcal/mole for dispersion in the reaction of cyclopentadiene with p-benzoquinone (Wassermann, 1965). These nonbonding attractive energies cooperate with the secondary HMO effects discussed earlier to lead to an endo product. 

Another consequence of the stronger interactions upon ionization is that the equilibrium geometry of the ionized complex may differ significantly from that of the neutral states. Broadened ionization onsets are frequently attributed to the spectral superposition of ionization into several vibrational levels for which Franck-Condon factors are more favorable.261 As a result, the adiabatic ionization potential may be considerably lower than the vertical potential, and the observed ionization onsets may occur above the adiabatic potential. Another factor to be considered is the conformation-dependent effect,213 due to the different conformations of the solvent molecules. The most populated form of a complex may involve a less stable form of the solvent. After photoionisation, the lowest-energy dissociation channel in the complex ion leads to the most stable form of isolated solvent, which has to be taken into account for the estimate of the binding energy. 

The 2D-NMR NOESY correlations determined the absolute configuration (3S) for spirodioxocin 641a, which could adopt different conformations whose relative populations depended on steric factors, anomeric, and related effects and intramolecular //-bonding. In the preferred conformation of 641a, both endocyclic oxygen atoms were disposed in equatorial position relative to the other cycle and, therefore, such a structure was not stabilized by a conformational anomeric effect. The conformation (3Y)-641 a that disposed both endocyclic oxygen atoms in an axial position, which was stabilized by a double conformational anomeric effect, would imply chair-chair conformation for... 

Since before the turn of the century it has been known that the optical activity of some chiral compounds is solvent dependent (1 ). For example, in 1877 Landolt (2) reported that the specific rotations of (+)-camphor, (-)-nicotine, (+)-diethyl tartrate, and (-)-turpentine varied with solvent and concentration. In the last decade there has been renewed interest in this solvent dependence. A number of different types of organic compounds has been investigated and the results have been interpreted in terms of variations in conformer populations that have resulted from either the effect of the dielectric on coulombic interactions between dipolar groups in the molecule (3), or from hydrogen-bond interactions between the solvent and the chiral solute (k). 

The observed diastereoselectivity has been rationalized on the basis of a kinetic anomeric effect which increases the reactivity of some conformers. and on steric factors which determine conformer population and dictate the direction of attack. The fundamental role of the tetrahy-drofuran ring oxygen in the nitrone is confirmed by the sluggish and stereorandom cycloadditions of analogs which possess a methylene group instead of Ihe furan oxygen55. 

The conformational effect of the aglycon in alkyl glycopyranosides has been examined with the methyl, ethyl, isopropyl, and tert-butyl tri-0-acetyl-/3-D-ribopyranosides, and the corresponding benzoates. In each series, there was a negligible change in conformational population as between the methyl, ethyl, and isopropyl derivatives, but the terf-butyl derivatives contained somewhat less of that con-former [IC(d)] having the aglycon axially attached, presumably because there is loss of some rotational freedom about the C-1-0-1 bond in the tert-butyl derivatives as a result of steric hindrance. 

From a consideration of detailed results on the conformational equilibria of aldopentopyranose derivatives, it has been pointed out92- 9 that a more sophisticated model is required before conformational populations can be reliably predicted, at least with acylated derivatives. Even with adjustment of the original parameters in order to take revised values for the anomeric equilibrium of D-lyxopyranose tetraacetate and the conformational equilibrium of /3-D-arabinopyranose tetraacetate into account, the observed data cannot be accommodated within the framework of this model, except on a very broad, qualitative basis. Other possible factors that should be considered " include polar contributions from substituents other than that on C-1, attractive interactions between syn-diaxial acyloxy groups, non-bonded interactions between atoms that have unshared pairs of electrons,repulsive interactions between gauche-vicinal groups, the effect of solvent pressure, and differences between the molar volume of conformers. 

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