Small molecule solvation

In the last several years, improved alchemical methodologies and increased computer power have made it possible to compute the free energies of large sets of small molecules wifh precision of less than 0.1 kcal/mol, sufficient to verify the validity of force-field parameters for small molecules [38,64,104-110]. Similar gains in efficiency were obtained for small molecule solvation through variations on Monte Carlo sampling of the Gibbs ensemble [111-114]. 

The ions in solution are subject to two types of forces those of interaction with the solvent (solvation) and those of electrostatic interaction with other ions. The interionic forces decrease as the solution is made more dilute and the mean distance between the ions increases in highly dilute solutions their contribution is small. However, solvation occurs even in highly dilute solutions, since each ion is always surrounded by solvent molecules. This implies that the solvation energy, which to a first approximation is independent of concentration, is included in the standard chemical potential and has no influence on the activity. 

This approach may be possible for small molecules because the gas-phase proton affinity can be obtained quantum mechanically with an accuracy of 1-2 kcal/mol [19]. However, the solvation free energy of H+ cannot be calculated and the experimental value is only known approximately, from 259.5 to 262.5 kcal/mol [60]. Also, because the proton affinity and solvation free energies in Eq. (10-7) are on the order of hundreds of kcal/mol, small percentage errors in the calculation can give rise to large error in AGaqP and pKa. Thus, this method for calculation of absolute pifa s remains impractical at the present time [6],... 

Another method to obtain absolute pKa s for small molecules is to compute deprotonation free energy directly from the free energies of species in the reaction using quantum mechanical and continuum solvation methods (Eq. 10-1),... 

We should thus expect the equilibrium to be shifted to the left compared with that for methanoic acid/methanoate anion, and it is in fact found that the pKa of ethanoic acid is 4-76, compared with 3-77 for methanoic acid. However, the degree of structural change effected in so small a molecule as methanoic acid by replacement of H by CH3 makes it doubtful whether so simple an argument is really valid it could well be that the relative solvation possibilities in the two cases are markedly affected by the considerably different shapes of, as well as by the relative charge distribution in, the two small molecules. 

The several theoretical and/or simulation methods developed for modelling the solvation phenomena can be applied to the treatment of solvent effects on chemical reactivity. A variety of systems - ranging from small molecules to very large ones, such as biomolecules [236-238], biological membranes [239] and polymers [240] -and problems - mechanism of organic reactions [25, 79, 223, 241-247], chemical reactions in supercritical fluids [216, 248-250], ultrafast spectroscopy [251-255], electrochemical processes [256, 257], proton transfer [74, 75, 231], electron transfer [76, 77, 104, 258-261], charge transfer reactions and complexes [262-264], molecular and ionic spectra and excited states [24, 265-268], solvent-induced polarizability [221, 269], reaction dynamics [28, 78, 270-276], isomerization [110, 277-279], tautomeric equilibrium [280-282], conformational changes [283], dissociation reactions [199, 200, 227], stability [284] - have been treated by these techniques. Some of these... 

The solvation models are used to predict the properties of small molecules and large biomolecules employing different levels of theory. In the prediction of solvent effect using electronic structure calculation, semiempirical, HF, post-HF, and DFT-based hybrid methods have been widely used [2-11], Since a wealth of literature is... 

However, picosecond resolution is insufficient to fully describe solvation dynamics. In fact, computer simulations have shown that in small-molecule solvents (e.g. acetonitrile, water, methyl chloride), the ultrafast part of solvation dynamics (< 300 fs) can be assigned to inertial motion of solvent molecules belonging to the first solvation layer, and can be described by a Gaussian func-tiona) b). An exponential term (or a sum of exponentials) must be added to take into account the contribution of rotational and translational diffusion motions. Therefore, C(t) can be written in the following form ... 

LiC104. this produces materials with remarkably high conductivities 1.7 X 10" at 20°C and 1.1 x 10" at — 10°C (Abraham and Alamgir, 1990). The small molecule appears to serve two functions it may plasticise the host polymer and thereby induce flexibility and segmental motion in the host polymer chains, and it solvates the cation, or more rarely an anion, (thereby reducing ion-ion interactions). 

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