Local cosolvent effect

Solubility can also be enhanced by the presence of other compounds. This phenomenon is caused by one or more compounds acting as solubility enhancers for other compounds present on a surface. This phenomenon is sometimes called the local cosolvent effect. A typical method of enhancing contaminant solubility is through the addition of a small amount of secondary solvent to the SCF cleaning system. Alcohols are commonly used in this manner to increase solubilities of more polar contaminants. However, more subtle local cosolvent effects have been observed. Perhaps a classic example was first reported by Kumik and Reid. In their study, they observed that the solubilities of both naphthalene and benzoic acid in supercritical CO2 were enhanced by 107% and 280%, respectively, when both species were present. It has also been shown that there needs to be enough of a secondary component present in solution about the local contaminant environment to enhance the solubility of another compound, This example demonstrated that an excess of phenanthrene promoted the solubility of anthracene in supercritical COj, but since anthracene was only present in very small quantities, it did not help to enhance the overall solubility of phenanthrene. A... 

BL Knutson, SH Sherman, KL Bennett, CL Liotta, CA Eckert. Benzophenone as a probe of local cosolvent effects in supercritical ethane. Ind Eng Chem Res 36 854, 1997. 

Smith PE (2004) Local chemical potential equalization model for cosolvent effects on biomolecular equilibria. J Phys Chem B 108(41) 16271-16278... 

Proton transfer is sensitive to the local solute environment in liquid solutions as evidenced by the water quenching curves for 2-naphthol and its cyano- derivatives. We have used proton transfer as a mechanism to probe the cosolvent composition around a solute in supercritical fluids to discern any difference between local and bulk concentrations. No proton transfer was observed from either 2-naphthol or 5-cyano-2-naphthol, presumably indicating insufficient structure in the SCF to solvate the proton. Although significant cosolvent effects on the fluorescence emission were observed, these appear to be independent of the thermodynamic variables. 

Preparations that are applied topically to the mouth and throat have contained glycerin, ethanol, propylene glycol, and PEG. Both systemic and local toxic effects would need to be considered in choosing a solvent system for these preparations. Table 6 contains a list of dermal and topical mouth and throat products that contain cosolvents. 

Knutson et al. (280) measured the kinetics of the Diels-Alder reaction of maleic anhydride (MA) and 2,3-dimethyl-1,3-butadiene (DMB) in SCF propane solutions at 100-140°C and 46-141 bar. Reaction to the product 4,5-dimethyl-CM-l,2,3,6-tetrahydrophthalic anhydride (DMTA) was evaluated with excess DMB as a reactive cosolvent and 2,2,2-trifluoroethanol (TFE) as an unreac-tive cosolvent (Scheme 21). Near-critical effects and cosolvent effects on reaction rates were analyzed from transition state theory. Rate constants increased with increasing pressure at 140 C, but were not significantly affected at 100°C and 120 C at near-critical densities. A similar lack of pressure dependence has been reported by Reaves and Roberts (281) for the Diels-Alder reaction of MA with isoprene in subcritical propane at 80°C. This minimal pressure effect is in contrast to those noted above for Diels-Alder reactions in SCCO2 where the reactants were at approximately equal and dilute concentrations. The influence of the unreactive cosolvent, TFT, on reaction rates was found to be minimal. These results suggest that the local reactant composition, as well as pressure, temperature, and cosolvent, can be used to control the reaction rate of such reactions in the near-critical region. 

In supercritical fluids, the possibility of local composition enhancements of cosolvent about a solute suggests that we should see enhancement of anion fluorescence if the water cosolvent clusters effectively about the 2-naphthol solute. Although in liquids the water concentration must be >30% to see anion emission, the higher diffusivity and density fluctuations in SCFs could allow stabilization of the anion at much lower water concentrations provided that the water molecules provide sufficient structure. Therefore the purpose of these experiments was to investigate 2-naphthol fluorescence in supercritical CO 2 with water cosolvent in the highly compressible region of the mixture to probe the local environment about the solute. 

Solvation in supercritical fluids depends on the interactions between the solute molecules and die supercritical fluid medium. For example, in pure supercritical fluids, solute solubility depends upon density (1-3). Moreover, because the density of supercritical fluids may be increased significantly by small pressure increases, one may employ pressure to control solubility. Thus, this density-dependent solubility enhancement may be used to effect separations based on differences in solute volatilities (4,5). Enhancements in both solute solubility and separation selectivity have also been realized by addition of cosolvents (sometimes called entrainers or modifiers) (6-9). From these studies, it is thought that the solubility enhancements are due to the increased local density of the solvent mixtures, as well as specific interactions (e.g., hydrogen bonding) between the solute and the cosolvent (10). 

Considerable interest exists in the local effects that cosolvents exert during IV and intramuscular (IM) injection. Several investigations have studied the... 

Equations for the KBIs in ternary mixtures are available in matrix form [2]. Explicit equations are obtained here which will allow us to analyze interesting features of ternary mixtures, such as the effect of a third component on the phase behavior of a binary mixture and the effect of a cosolvent (entrainer) on supercritical binary mixtures. Only the former problem is examined in the present paper. The calculations will he carried out for an interesting ternary mixture, namely AA -dimethylformamide-methanol-water, in order to extract information about the intermolecular interactions. In the next section explicit equations for the KB integrals will he derived and applied to the above ternary mixture. Finally, the results obtained will be used to shed some light on the local structure and the intermolecular interactions in the above mixture. 

The knowledge of the Kirkwood-Buff integrals for dilute mixtures can be very helpful in the analysis of the local water/cosolvent composition in the vicinity of a solute molecule. Ultimately, it can provide information about the effect of various cosolvents on the protein behavior in aqueous solutions. 

In this paper, the Kirkwood-Buff theory of solutions is used to examine the effect of PEG on aqueous protein solutions, the focus being on the local composition of the mixed solvent in the vicinity of the protein molecule and on the protein solubility. The theoretical considerations led to equations that coimect the experimental preferential binding parameter with the excess (or deficit) numbers of water and cosolvent molecules around a protein molecule. Calculations were carried out for various proteins in various PEG solutions. The results showed that in all cases the proteins were preferentially hydrated. Evidence was also brought that the hydration is a result of steric exclusion. 

Foster and coworkers measured the solubility of hydroxybenzoic acid in supercritical CO2 with 3.5 mol % methanol or acetone as a cosolvent and found enhancements that were beyond the effects of the density increases from neat CO2 to the mixtures (148). They attributed the solubility enhancements to a higher local concentration of cosolvent molecules around the solute and even estimated the local mixture compositions in terms of the experimental solubility data. 

Brennecke and coworkers (90,320) investigated the uncatalyzed esterification of phthalic anhydride with methanol in SCCO2 as a probe reaction to show that augmented local densities and cosolvent compositions in the near-critical region represent enhanced reactant concentrations that result in increased reaction rates. The authors report kinetic data for the esterification reaction at both 40 C and 50 C and pressures ranging from 97.5 to 166.5 bar. Based on bulk fluid compositions, a dramatic pressure effect was exhibited for the measured bimolecular rate constants. For example, at 50°C the value of the rate constant decreased 25-fold from 0.0348 L/mol-min at 97.5 bar to 0.00138 L/mol-min at 166.5 bar, which represents one of the largest pressure effects ever reported for a reaction in an SCF. Based on calculations of the thermodynamic pressure effect on the rate constant from transition state theory and estimates of the local concentrations from literature data, the authors conclude that the dramatic pressure... 

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