Solvent Effects on Conformational Equilibria

For example, the standard molar Gibbs energy for the rotational equilibrium (30a) (30b) of chloroacetaldehyde is strongly solvent-dependent, as shown in Table 4-7 [87]. 

Inspection of Table 4-7 reveals a substantial increase in the more dipolar rotamer (30b) as the polarity of the solvent increases. In saturated hydrocarbon solvents (the 

Another remarkable example is the medium effect on the rotational equilibrium of ethoxycarbonylmethylene triphenylphosphorane (31a) (31b). As the polarity of the solvent increases, the equilibrium shifts in the direction of the s-trans-isovaev (31b), as shown by the equilibrium constants presented in Table 4-8. 

Addition of the extremely polar lithium bromide favours the formation of the s-trans isomer even more [95]. Analogous results were obtained with formylbenzylidene triphenylphosphorane [96]. 

In this context, the solvent influence on the C—N rotational barrier in N,N-dimethylformamide, Mc2N—CH=0 - Me2N+=CH—0 , is noteworthy [280]. For this rotation, the Gibbs free energy of activation in the gas phase AG =81 kJ/mol) is much smaller than in polar HBD solvents such as water AG = 92 kJ/mol). Thus, the rate of amide bond rotation decreases as the polarity and the HBD ability of the solvent increases. This can be attributed to the change in dipole moment on rotation, whereby a polar solvent stabilizes the ground state with the higher dipole moment fi = 3.8 D) in preference to the less dipolar activated complex [280]. 

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Foresman et al.175 applied the DFT(B3LYP)/SCRF calculations to obtain the polar solvent effect on conformational equilibria in furfuraldehyde and on the C-C rotational barrier of (2-nitrovinyl)amine. The authors demonstrated that the poor results obtained using either spherical or ellipsoidal cavities can be significantly improved upon performing the SCRF calculations for the cavity of molecular shape. 

Professor Lemieux recalls the following incident from this period. In connection with studies then being performed on solvent effects on conformational equilibria, Dr. Mills suggested that 1,2-O-isopropyli-dene 4-0-methyl-/3-L-sorbopyranose should be examined. The ex-... 

THEORETICAL EVALUATION OF SOLVENT EFFECT ON CONFORMATIONAL EQUILIBRIA OF SUGARS... 

Solvent effects on conformational equilibria can be pronounced, with higher populations of more polar isomers in polar solvents. This is reflected in Bell s expression for the free energy of solvation of a dipole fx with radius / in a continuum with dielectric constant e. ... 

Vitalis, A., Wang, X., Pappu, R.V. Atomistic simulations of the effects of polyglutamine chain length and solvent quality on conformational equilibria and spontaneous homodimerization. J. Mol. Biol. 2008, 384, 279-97. 

The purpose of this research was to compare the effect on the conformational equilibrium for the hydroxylated compounds listed in Table II of changing the solvent from dimethyl sulfoxide, which is expected to minimize intramolecular hydrogen bonding, to 1,2-dichloroethane which should promote such bonds. These solvation effects on conformational equilibria were then to be compared with those of water which can serve as a hydrogen donor and hydrogen acceptor in hydrogen bond formation. As will be seen, the conformational equilibria generally appear similar for water and dimethyl sulfoxide but often different from those in 1,2-dichloroethane. 

Gas-phase NMR spectroscopy has been used to obtain equilibrium constants and rate constants for many low-energy molecular processes. These data have been used to address questions regarding the relative stability of conformers and tautomers in the gas phase, the kinetics of exchange processes in the gas phase, and the direction and magnitude of solvent effects on these equilibria and processes. Most of the studies have appeared in the last 10 years. Continued progress in NMR instrumentation and techniques as well as considerable recent developments in kinetic theory ensure that the next 10 years will see many novel applications of gas-phase NMR spectroscopy. 

Abraham et al., who add an extra term to Equation 19 to allow for direct dipolar interactions between solvent and solute (17). This term is small for solvents of low dielectric constant but becomes significant for those having b> 10. The theory, thus modified, seems to give fairly satisfactory descriptions of polar effects on conformational equilibria (18), free energies of transfer of ion-pairs (19), and activation free energies of reactions . 

Dreyfus, M., Fires, J., Tauc, P., and Herve, G., Solvent effects on allosteric equilibria Stabilization of T and R conformations of Escherichia coh aspartate transcarbamylase by organic solvents, Biocbem., 23 4852-4859, 1984. 

Monte Carlo simulation techniques have been extensively used to study solvent effects on molecular properties and equilibrium points. Jorgensen has summarized theoretical work of condensed-phase effects on conformational equilibria [63]. 

Use of the combined QM/MM model for studying conformational equilibria has been described by Warshel, Jorgensen, 8o and by Field, Bash, and Karplus.35 The first computer simulation of the solvent effects on conformational equilibrium with a combined QM/MM approach, however, was carried out in 1992 in the investigation of the relative basicity of the syn and anti lone pairs of acetate ion in water. 81 In recognizing that the basicity difference... 

Both blocked anndno acids were found to be interfacially active. Their conformational preferences at the interface differ from those in the adjacent bulk phases and cannot be deduced from the stabilities of different conformers in these phases. This indicates that the interface exerts a unique effect on conformational equilibria in a single peptide unit. The orientations of the peptides are also affected. Nonpolar NANML is oriented such that its nonpolar side chain is buried in hexane, whereas the polar side chain of NANMQ is exposed to water. The free energies needed to rotate each peptide such that its side chain is immersed in the solvent of different polarity is substantial. 

Conformational Equilibria. The solvent effect on the conformational equilibria represents a typical problem studied using the DFT/SCRF methods. The presence of the environment may affect the free energy of a given conformer, its equilibrium conformation or even destabilize a particular conformation. The DFT/SCRF calculations have been applied to study such effects using various KS methods as well as different techniques for calculating [Pg.112]

At a more detailed level, we note that the solvent effects on the optical rotation have the same origins as solvent effects on the energy itself, as described in detail in other contributions to this book. Most other studies of solvent effects on natural optical activity have focused on the electrostatic contributions. These contributions can be partitioned into direct effects arising from the influence of the dielectric environment on the electronic density of the solute, and into indirect effects arising from the relaxation of the nuclear structure in the solvent. For conformationally flexible molecules, we may also consider a third possible solvent effect due to the changes in the conformational equilibria when going from the gas phase to solution. 

Dielectric continuum models such as the Generalized Born Solvent Accessible Surface Area (GB/SA) model are, in conjunction with force fields, excellent tools for fast and reliable calculations of hydration energies and solvent effects on, e.g., conformational equilibria and ligand-receptor interactions. The performance for neutral solutes is very good, whereas calculations on ionic compounds are currently more problematic. A solution to these problems most probably requires force fields that include polarization effects. For optimal accuracy of calculations using a dielectric continuum model, it is a clear advantage if the model is parameterized for the particular force field used. 

EXPERIMENTAL EVIDENCE OF SOLVENT EFFECT ON OLIGOSACCHARIDE CONFORMATIONAL EQUILIBRIA... 

The same group has investigated medium effects on the conformational equilibria of halogenocyclohexanes. A model of fixed cyclohexane geometry and constant C-hal bond dipole moment has been employed to calculate the dipole moments and solvent dependence of conformational equilibria of a series of mono- and di-halogenocyclohexanes. It is then possible to calculate the vapour state —AG values. 

Nitrogen J couplings are peculiarly valuable in structure determination because of their sensitivity to the presence and orientation of a lone pair on the nitrogen. Thus they are usually diagnostic of coordination, chelation, protonation, or hydrogen bonding of the nitrogen, and reflect departures from planarity, conformational relationships, syn-anti or cis-trans stereochemistry, solvent effects and solution equilibria, and so on. 

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