Solvophobic retention model

This is the so-called solvophobic retention model. The analyte is forced to leave a strongly cohesive mobile phase, where it interrupts the internal molecular (mainly hydrogen-bonding) interaction due to its less polar structure, in order to be absorbed into a new cavity in the less cohesive alkyl interphase, which is closer to its own polarity. 

Figure 2.4 (a) Solvophobic and (b) partitioning models of solute retention. 

In common with other polar solutes, peptide-nonpolar stationary phase interactions can be discussed in terms of a solvophobic model. In this treatment solute retention is considered to arise due to the exclusion of the solute molecules from a more polar mobile phase with concomitant adsorption to the hydrocarbonaceous bonded ligand, where they are held by relatively weak dispersion forces until an appropriate decrease in mobile-phase polarity occurs. This process can be regarded as being en-tropically driven and endothermic, i.e., both AS and AH are positive. 

In spite of widespread applications, the exact mechanism of retention in reversed-phase chromatography is still controversial. Various theoretical models of retention for RPC were suggested, such as the model using the Hildebrand solubility parameter theory [32,51-53], or the model supported by the concept of molecular connectivity [54], models based on the solvophobic theory [55,56) or on the molecular statistical theory [57j. Unfortunately, sophisticated models introduce a number of physicochemical constants, which are often not known or are difficult and time-consuming to determine, so that such models are not very suitable for rapid prediction of retention data. 

One popular model of retention has been the solvophobic theory, which relates retention to the surface tension of the mobile-phase solvents (103). As important as the solvophobic theory has been to the development of modern LC, it is based on an incorrect model of the relevant solution processes. It supposes that retention can be modeled in terms of the association of two solute molecules in a single solvent rather than on the transfer of a solute from one solvent to another. Hence the solvophobic theory does not take cognizance of the interactions of the solute with the second solvent, the cavity in the stationary phase it takes into account only the cavity in the mobile phase. 

The cavity model of solvation provides the basis for a number of additional models used to explain retention in reversed-phase chromatography. The main approaches are represented by solvophobic theory [282-286] and lattice theories based on statistical thermodynamics [287-291]. To a lesser extent classical thermodynamics combining partition and displacement models [292] and the phenomenological model of solvent effects [293] have also been used. Compared with the solvation parameter model all these models are mathematically complex, and often require the input of system variables that are either unknown or difficult to calculate, particularly for polar compounds. For this reason, and because of a failure to provide a simple conceptual picture of the retention process in familiar chromatographic terms, these models have largely remained the province of the physical chemist. 

HiPac (53) from Phase Separation is another commercially available software package. In several aspects this software is similar to DryLab, but its most important feature is that it can estimate the optimum mobile-phase conditions for the separation of the mixture at hand or only a selected number of peaks. Recently, ChromSword (commercially available from Merck, Germany) was introduced (34). It uses a retention mc el based on solvophobic theory. The input for this package can be the structural formulas of the solutes, the combination of structural formulas and retention data from a single run, or retention data from two runs. Data from additional runs are incorporated into the model, and prediction accuracy below 3% can be achieved under these circumstances. 

The retention process in RPC and HIC can be described from a number of theoretical perspectives, either in terms of rigorously consistent treatments based on the thennodynamics of interaction or from more empirical considerations. Of the approaches that have gained currency, the solvophobic theory [149,150], the close-contact model [151-153] with the interactions based on van der Waals and other short-range forces, and the stoichiometric solvent displacement model [154,155] have attracted the most interest. All theories assume that near-equilibrium conditions are achieved in the interactions of proteins or peptides with the nonpolar ligates. In most models, the factors affecting the magnitude of the changes in retention have been assumed to be either independent or. 

Fig. 3. Retention in reversed-phase chromatography according to the model of interphase and solvophobic effects. Due to the elevated cohesion energy density within the partly aqueous mobile phase, the energy liberated upon closing a cavity therein exceeds the energy required to create a new cavity within the less cohesive alkyl chain interphase.

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