Solvophobic theory

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 

Several other models have been proposed to account for retention in reversed phase chromatography of these two have found some degree of popularity and include the concepts of molecular connectivity and interaction indexes . The value of the molecular connectivity index has been shown to be proportional to the capacity ratio and the solubility of the solute in water (Karger et al., 1976). 

The interaction index is somewhat similar to Snyder s polarity index, P, although significant differences are observable with polar compounds (Jandera et al., 1982). The interaction index defines the interactions between the solute and the mobile phase and the model demonstrates that there is a quadratic relationship between the log of the capacity ratio and the volume fraction of organic solvent in the eluent. A consequence of this model is that there is a linear relationship between the corrected log of the capacity ratio log k = (log k — log / )/Fx and the interaction index, where is the phase ratio and is the molar volume of the solvent. The retention of a specific solute may therefore be predicted from the interaction index of the solute and specific physical parameters of the solvent. This model has been used to accurately determine the retention behaviour of solutes in both binary and ternary solvent systems (Jandera et al., 1982 Colin et al., 1983a). 

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The solvophobic model of Hquid-phase nonideaHty takes into account solute—solvent interactions on the molecular level. In this view, all dissolved molecules expose microsurface area to the surrounding solvent and are acted on by the so-called solvophobic forces (41). These forces, which involve both enthalpy and entropy effects, are described generally by a branch of solution thermodynamics known as solvophobic theory. This general solution interaction approach takes into account the effect of the solvent on partitioning by considering two hypothetical steps. Eirst, cavities in the solvent must be created to contain the partitioned species. Second, the partitioned species is placed in the cavities, where interactions can occur with the surrounding solvent. The idea of solvophobic forces has been used to estimate such diverse physical properties as absorbabiHty, Henry s constant, and aqueous solubiHty (41—44). A principal drawback is calculational complexity and difficulty of finding values for the model input parameters. 

Retention in HIC can be described in terms of the solvophobic theory, in which the change in free energy on protein binding to the stationary phase with the salt concentration in the mobile phase is determined mainly by the contact surface area between the protein and stationary phase and the nature of the salt as measured by its propensity to increase the surface tension of aqueous solutions [331,333-338]. In simple terms the solvopbobic theory predicts that the log u ithn of the capacity factor should be linearly dependent on the surface tension of the mobile phase, which in turn, is a llne2u function of the salt concentration. At sufficiently high salt concentration the electrostatic contribution to retention can be considered constant, and in the absence of specific salt-protein interactions, log k should depend linearly on salt concentration as described by equation (4.21)... 

Separations in hydrophobic interaction chromatography have been modeled as a function of the ionic strength of the buffer and of the hydrophobicity of the column, and tested using the elution of lysozyme and ovalbumin from octyl-, butyl- and phenyl-Sepharose phases.2 The theoretical framework used preferential interaction analysis, a theory competitive to solvophobic theory. Solvophobic theory views protein-surface interaction as a two-step process. In this model, the protein appears in a cavity in the water formed above the adsorption site and then adsorbs to the phase, with the free energy change... 

A nonpolar neutral species in a polar medium such as water experiences interfacial tension. Solvophobic theory is a general statement of hydrophobic theory, which has been developed to explain the tendency of neutral organic species to flee the water phase. It has been reported that the solution of nonelectrolytes in water is attended by a net decrease in entropy [65,158]. This has been attributed to an increased structuring of water molecules in the vicinity of the solute. The process may be conceptually rationalized by considering that a solute must occupy space in a cohesive medium. The solute must create a cavity in the water milieu and then occupy that cavity [19,65,158]. The very high cohesive density of water creates considerable interfacial tension in the... 

Molnar, 1., Searching for robust HPLC methods—Csaba Horvath and the solvophobic theory, Chwmatographia, 62, 549, 2005. 

The thermodynamics of solute interaction with nonpolar ligates of the stationary phase will be treated later in this chapter within the framework of the solvophobic theory 107-108). According to this theoretical approach the equilibrium constant for the reversible binding of a given eluite to the hydrocarbonaceous ligates at fixed eluent properties and temperature can be approximated by the relationship... 

Fig. 38. The process of going into solution is treated as two steps in the solvophobic theory. The first step is the creation of a cavity of size and shape suitable for (he incoming solute. In the second step the solute enters the cavity and interacts with the surrounding solvent. Reprinted from Horvith and Melander (139). J. Chromatogr. Scl.. with permission from Reston niblications.

The solvophobic theory has been successfully applied to treat the effect of solute ionizatiqn as well as the effect of salts on the retention of both neutral and ionized species. There is ample experimental evidence that retention of a spfeies decreases upon ionization according to the theoretical prediction. Addition of salts to aqueous eluents increases surface tension and consequently. the retention of neutral eluites on nonpolar stationary phases. With ioni d solutes, however, the solvophobic theory predicts a minimum at low ionic strength in plots of retention versus ionic strength and this phenomenon has also been experimentally demonstrated. 

Solvents, UV cut-olf values, 70 Solvents, miscibility, 75 Solvophobic effect, 201,203 Solvophobic inleHlclidHk, IS2, 20i Solvophobic ion chromatography, 242 Solvophobic theory, 141,148,152,155, 158, 202, 203, 226, 228, 246 8omatostedn, 263,290 Sorbents, polymeric, 127 Sorption isottom, 159 Soiption kineties, efbet on column effi-cieney in RPC, 227 Speed of aepantion, optimization [Pg.172]

Factors that influence the retentive powers and selectivity of such bonded phases include the surface concentrations of hydrodartenaceous ligates and free silanol groups. The thermodynamic aspectitm solute interactions with the hydrocarbonaceous ligates at the surface, which are hydrophobic interactions in the case of aqueous eluents, are discussed later in this chapter within the framework of the solvophobic theory. In practice, however, solute interactions with surface silanol which may be termed silanophilic interactions can also contribute ]to retention (71, 75, 93), particularly in the case of amino compounds. Consequently the retention mechanism may be different from that which would be ol served with an ideal nonpolar phase. Therefore, increasing attention is paid to the estimation of the concentration of accessible sianols and to their elimination from the surface of bonded phases. 

The solvophobic theory could be extended to the treatment of other special effects such as hydrogen bonding between eluite and species. present in the eluent. The predictive power of the theory may be improved by such extension. In addition a rigorous theory for treatment eluite interaction with surface silanols would be needed. 

The theoretical treatment of the hydrophobic effect is limited to pure aqueous systems. To describe chromatographic separations in RPC Horvath and Melander developed the solvophobic theory [47]. In this theory, no special assumptions are made about the properties of solute and solvent, and besides hydrophobic interaction electrostatic and other specific interactions are included. The theory has been valuable to describe the retention of nonpolar [48], polar [49], and ionizable [50] solutes in RPC. The modulation of selectivity via secondary equilibria (variation of pH, ion pair formation [51]) can also be described. On the other hand, it is not a problem to find examples of dispersive interactions in literature, e.g., separation of carotinoids with a long chain (C30) RP gives a higher selectivity compared to standard RP C18 cyclohexanols are preferentially retarded on cyclohexyl-bonded phases compared to phases with linear-bonded alkyl groups. 

As is evident from the above discussion, the composition and primary structure of the peptide as well as the characteristics of the mobile and stationary phases all play critical roles in determining the magnitude of retention in RPC. Solvophobic theory 17 39 40 47 56 69-71 can be... 

The retention mechanism is not yet fully understood. The solvophobic theory does not account for any interaction in the stationary phase, which plays a passive role. The partition mechanism as described by Dill and Dorsey (27) is generally accepted. The most relevant feature is the linear plot of In k versus carbon number in a homologous series (Fig. 10), which is similar to what is observed in isothermal gas-liquid chromatography. Retention is governed mainly by hydro-... 

The sample diluent affects the solute dispersion. If we consider the effects of three different diluents (hexane, chloroform, and acetone) on the chromatographic behavior of a TG mixture on RP columns using, for example, acetonitrile and ethanol as the mobile phase, we can see that the TGs dissolved in hexane provided only a minute chromatographic trace, whereas dissolution in chloroform yielded excellent detection and resolution. These results can best be explained by invoking the solvophobic theory of Horvath and Melander (85). 

Two main theories, the so-called solvophobic and partitioning theories, have been developed to explain the separation mechanism on chemically bonded, non-polar phases, as illustrated in Figure 2.4. In the solvophobic theory the stationary phase is thought to behave more like a solid than a liquid, and retention is considered to be related primarily to hydrophobic interactions between the solutes and the mobile phase14-16 (solvophobic effects). Because of the solvophobic effects, the solute binds to the surface of the stationary phase, thereby reducing the surface area of analyte exposed to the mobile phase. Adsorption increases as the surface tension of the mobile phase increases.17 Hence, solutes are retained more as a result... 

The wide use of these bonded phases has also stimulated a large effort to explain their surface structure and how they work. The so-called solvophobic theory of RPLC was elaborated originally by Horvath and Me-lander.16 Their model assumes that the nonpolar bonded phase acts more like a solid than a liquid and attracts analytes by adsorption. The binding of an analyte to the surface reduces the surface area of the analyte exposed to the mobile phase, and it can be considered to be sorbed partially because of this solvent effect that is, the analyte is sorbed because it, is solvophobic. Sorption increases as the surface tension of the mobile phase increases. 

Solvophobic theory provides a theoretical framework to evaluate hydrophobic effects. To place a polypeptide or protein into a solvent, a cavity of the same molecular dimensions must first be created. The amount of energy or work required to create this cavity is related to the cohesive energy density or the surface tension of the solvent. The fusion of cavities reduces the total surface area in the combined cavity, and thus the free energy of the... 

Meliander, W. R., Corradini, D., and Horvath, C. (1984). Salt-medated retention of proteins in hydrophobic-interaction chromatography. Application of solvophobic theory. J. Chromatogr. 317, 67-85. 

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