Relative solvation free energy

The free energy of activation at the QCISD(T)/6-31 H-- -G(d,p) level amounts to 21.1 kcal/mol. According to the authors, the large electron density redistribution arising upon cyclization makes it necessary to use extended basis sets and high-order electron correlation methods to describe the gas-phase thermodynamics, which indicates clearly the gas-phase preference of the azido species. However, the equilibrium is shifted toward the tetrazole as the polarity of a solvent is increased. For instance, SCRF calculations (e = 78.4) yield a relative free energy of solvation with respect to the cw-azido isomer of —2.4 kcal/mol for the tmns-zziAo compound and of —6.8 kcal/mol for the tetrazole isomer. At a much lower level, the... 

Fig. 2.5. Possible applications of a coupling parameter, A, in free energy calculations, (a) and (b) correspond, respectively, to simple and coupled modifications of torsional degrees of freedom, involved in the study of conformational equilibria (c) represents an intramolecular, end-to-end reaction coordinate that may be used, for instance, to model the folding of a short peptide (d) symbolizes the alteration of selected nonbonded interactions to estimate relative free energies, in the spirit of site-directed mutagenesis experiments (e) is a simple distance separating chemical species that can be employed in potential of mean force (PMF) calculations and (f) corresponds to the annihilation of selected nonbonded interactions for the estimation of e.g., free energies of solvation. In the examples (a), (b), and (e), the coupling parameter, A, is not independent of the Cartesian coordinates, x. Appropriate metric tensor correction should be considered through a relevant transformation into generalized coordinates...

Relative Free Energies of Solvation in Water, in kcal/mole, Obtained by Classical Discrete Molecular Solvent Methods... 

Relative Free Energies Of Solvation in Water, in kcal/mole," Obtained by a QM/MM Discrete Molecular Solvent Method, Using The AMI Solute Hamiltonian. The Estimated Error Bars for The Calculated Values Are 0.5 Kcal/Mole... 

Relative Free Energies of Solvation in Water, in kcal/molc. 

Further attempts have been made to explain and predict the proportions of the pyranose forms in solution. It is not difficult to calculate, by various methods, the relative free energies in vacuum or in inert solvents it is not, however, easy to take the effect of solvation into account. Clearly, solvation has a substantial effect on the composition, and the variation of the dielectric permittivity between different solvents does not fully account for this effect. 

Crown ethers continue to be one of the most useful parts of supramolecular chemistry/91 From the beginning computations of metal ions complexes with synthetic ionophores/101 which have been aptly reviewed/111 emphasized the importance of including explicitly solvation in free energy calculations, also with ab initio calculations on calixarene complexes/121 Molecular dynamics simulations of 18-crown-6 ether complexes in aqueous solutions predict too low affinities, but at least correctly reproduce the sequence trend K+ > Rb+ > Cs+ > Na+. However, only the selection of K+ over Rb+ and Cs+ is ascribed to the cation size relative to that of the crown cavity, whereas K+ appears in these calculations to be selected over Na+ as consequence of the greater free energy penalty involved in displacing water molecules ftomNa/1131... 

These two examples suffice to illustrate the dramatic effect of solvation on the tautomeric preferences. For our purposes here, it also worth noting the close similarity in the relative free energies of solvation determined from the QM-SCRF MST... 

Free energy perturbation calculations use Monte Carlo or molecular-dynamics approaches to calculate relative free energies (e.g., of solvation or host-guest binding) on the basis of thermodynamic cycles involving the binding processes of two related systems and the artificial mutation of one system into the other. 

With the NDDO methods, tautomeric equilibria,22o especially in heterocycles,216-219,223,224,227,232,233 have been a favorite topic for study using the BKO approach. The tautomeric equilibria of many heterocyclic systems are exquisitely sensitive to solvation,i i3>2i4 making them interesting test cases for the validation of any solvation model. A detailed comparison is presented later in the section on relative free energies in heterocyclic equilibria. A comprehensive study of the stabilization of a wide variety of carbon radical and ionic centers has also been reported.21 ... 

In fact, very large basis set, correlated calculations suggest that the CH tautomer is favored over the NH in the gas phase by only 6.2 kcal/mol. Assuming an approximately equal mixture of the two tautomers in aqueous solution,3i3 the AMI-SMIa model is within about 1 kcal/mol of correctly predicting the relative free energies of solvation. The more general AM1-SM2 model is not quite as accurate in its consideration of heteroatom-bound protons, and it thus provides a somewhat poorer prediction in this instance, although it remains closer than any of the other models. 

Cieplak, P. and P. Kollman (1990). Monte Carlo Simulation of Aqueous Solutions of Li+ and Na+ Using Many-Body Potentials. Coordination Numbers, Ion Solvation Enthalpies, and the Relative Free Energy of Solvation. I. Chem. Phvs. 921111 6761. 

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