COSMO application potential

As we have seen before, COSMO-RS is able to describe the chemical potentials of compounds in almost any pure or mixed liquid phase, as long as the chemical composition of the liquid is known and as long as it can be considered as a chemically homogeneous phase. While this has opened an enormously broad range of applications in chemical engineering, these limitations exclude COSMO-RS from a number of important application areas in environmental simulations, life-science modeling, and product development. 

Since COSMO-RS allows for a rather fundamental calculation of the chemical potential of molecules in various chemical environments, there are many application areas that go beyond the calculation of activity and partition coefficients, which are directly accessible from the differences of chemical potentials in different phases. Often, such applications require the addition of some empiricism to the model because they involve free-energy contributions that are not directly accessible by COSMO-RS. Nevertheless, in many cases, the COSMO-RS is a robust starting point for such empirical extensions, and the resulting models are still less empirical and more fundamental than many other approaches. Without going into details we will describe some extended application areas in this chapter. 

Indeed, prediction of the change of the equilibrium constants of a chemical reaction in a variable liquid environment requires nothing other than the prediction of the chemical potentials or activity coefficients of the starting materials and products in the liquids. Thus, this task can be performed simply by using the standard COSMO-RS capabilities. Successful applications of this... 

Since most other modeling techniques for polymers are extremely demanding, the limited capabilities of COSMO-RS for efficient prediction of solubilities in polymers can be of great help in practical applications when suitable polymers with certain solubility requirements are desired. One application may be the selection of appropriate membrane polymers for certain separation processes. Predictions of drug solubility in polymers are sometimes of interest for pharmaceutical applications. Furthermore, it is most likely that COSMO-RS can also be used to investigate the mutual compatibility of polymers for blends. This aspect, and many other aspects of the potential of COSMO-RS for polymer modeling, still awaits systematic investigation. 

Section 3 concerns the COSMO-RS approach. This is a theory that goes beyond the usual dielectric approximation, in contrast to all other CSMs, it treats solute and solvent on the same footing and it finally allows for the calculation of chemical potentials of molecules in almost arbitrary solvents. First, in Section 3.1 the principal inapplicability of the dielectric theory to electrostatic screening on a molecular scale is expounded. Section 3.2 gives the central COSMO-RS theory, i.e., an alternative ansatz for the interpretation of electrostatic screening of solutes in solvents and its combination with statistical thermodynamics. Section 3.3 illustrates the novel COSMO-RS view of solvation for some typical solvents, while Section 3.4 shows the potential of the approach using the results of a broad para-metrization and validation study. In Section 3.5 the range of applicability is outlined. 

The overall inaccuracy for the four properties is 1.7 kJ mol with respect to the chemical potentials, corresponding to a factor of 2 for the nonlogarithmic equilibrium constants. This is comparable with the results of incremental methods for the estimation of partition coefficients. Considering the relatively small number of parameters, the short history, and the broad applicability of the COSMO-RS approach, this accuracy is very satisfactory. Although there are several possibilities for further improvements of the approach, a substantial decrease of the inaccuracy below this factor of 2 will be hard to achieve. 

Because COSMO-RS is a quite general theory for pure or mixed fluid systems, which treats the solvent etnd the solutes on the same footing, it is applicable to a great variety of questions in chemistry. A special advantage of the COSMO-RS formalism is its computational efficiency, since the time-demanding COSMO calculations have only to be performed once per molecule, or once per relevant, electrostatically different conformation, while all variations of solvents, compositions, and temperature only require a recalculation of the a-potential. 

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