Solute-solvent interactions molecular surface area

When the solute molecule dissolves in the solvent two interactions are possible which produce a negative free energy change, these being Van der Waals and electrostatic interactions. The energy associated with the Van der Waals interactions is approximately proportional to the molecular surface area of the solute, while the electrostatic forces... 

A careful analysis of molecular structures led Dunn et al. to associate the two principal components with the two molecular parameters described in Figure 7, namely, the isotropic surface area (ISA), related to the solute surface accessible to nonspecific solvent interactions, and the solvent-accessible, hydrated surface area (HSA) associated with hydration of polar functional groups. 

Attempts have been made to distinguish between these theories on the basis of the AH° and values anticipated for the two theories, but it may be illusory to think of them as independent alternatives. The eavity model has been criticized on the basis that it eannot account for certain observations such as the denaturing effect of urea, but it must be noted that the cavity theory includes not only the cavity term AAy, but also a term (or terms) for the interaction of the solutes and the solvent. A more eogent objeetion might be to the extension of the macroseopic concepts of surface area and tension to the molecular scale. A demonstration of the validity of the cavity concept has been made with silanized glass beads, which aggregate in polar solvents and disperse in nonpolar solvents. 

The molecular volume descriptor, V, can be recognized as an important descriptor once one realizes that the free energy of solution is related in part to the size of the cavity that must be carved out of the solvent bath by the solute molecule during the solvation process. The surface area, A, of a molecule or a fragment of a molecule may be construed as a measure of the region available for interaction with another molecule. For computing V and A, one could use a particular electron density contour or a non-QM-derived measure of atomic size such as the van der Waals radii available from standard tables in physical chemistry textbooks. 

The most expensive part of a simulation of a system with explicit solvent is the computation of the long-range interactions because this scales as Consequently, a model that represents the solvent properties implicitly will considerably reduce the number of degrees of freedom of the system and thus also the computational cost. A variety of implicit water models has been developed for molecular simulations [56-60]. Explicit solvent can be replaced by a dipole-lattice model representation [60] or a continuum Poisson-Boltzmann approach [61], or less accurately, by a generalised Bom (GB) method [62] or semi-empirical model based on solvent accessible surface area [59]. Thermodynamic properties can often be well represented by such models, but dynamic properties suffer from the implicit representation. The molecular nature of the first hydration shell is important for some systems, and consequently, mixed models have been proposed, in which the solute is immersed in an explicit solvent sphere or shell surrounded by an implicit solvent continuum. A boundary potential is added that takes into account the influence of the van der Waals and the electrostatic interactions [63-67]. 

---