Aqueous/organic cosolvent systems

Solubility of the CDs is low in most organic solvents (Table 6). In aqueous/organic cosolvent systems, the solubility decreases as the organic concentration increases, with the exceptions of ethyl and propyl alcohol where a maximum is observed at around 30% alcohol. " ... 

Aqueous and aqueous-organic biphasic systems would constitute straightforward reaction mixtures for catalyzed hydration of olefins and alkynes. In fact, water is chemically utilized in telomerization of dienes with H2O (179) and hydration of alkynes has also gained synthetic importance (222). However, these reactions are usually run in homogeneous solutions making the olefin or alkyne soluble by using a water-miscible organic cosolvent (alcohols, THF). 

In the following text, examples of solvent effects on enzyme selectivity, referred either to systems based (i) on water-miscible organic cosolvents added to aqueous buffers or (ii) on organic media with low water activity, are discussed. 

The organic compounds were dissolved or dispersed in an aqueous solution of the catalyst, with or without an organic cosolvent, and the net oxidations were carried out at applied potentials causing the oxidation of Ru11 to RuIV complex (0.6-0.8 V vs. SCE). It has been demonstrated that this electrocatalytic system is capable of providing a general and selective method for the oxidation of alcohols, aldehydes, cyclic ketones, and C—11 bonds adjacent to alkeneic or aromatic groups. 

Drug dissociation constants are experimentally determined by manual or automated potentiometric titration or by spectrophotometric methods.40 Current methods allow determination of pXa values with drug concentrations as low as 10 to 100 pM. For highly insoluble compounds (concentration <1 to 10 pM), the Yesuda-Shedlovsky method41 is commonly used where organic cosolvents (i.e., methanol) are employed to improve solubility. The method takes three or more titrations at different cosolvent concentrations, and the result is then extrapolated to pure aqueous system. The dissociation constant can also be determined with less accuracy from the pH-solubility profile using the following modification of Henderson-Hasselbach equation ... 

Although determination of a complete pH-degradation rate profile is desired, it may not always be practical due to limitations of drug supply and time. Also, insufficient solubility in purely aqueous systems may limit determination of pH-degradation rate profiles. Organic cosolvents may be used to increase solubility however, extrapolation to aqueous conditions must be done with caution. Stability of the drug in a suspended form in the desired buffer can be tested in lieu of solution stability. The stress test results must however, be interpreted in relation to the solubility in the suspension medium. The test may provide an empirical indication of pH stability in the presence of excess water. Satisfactory stability in the GI pH range (1 to 7.5) is important for oral absorption. While there are examples of... 

A relatively weak rate enhancement was observed in the biphasic hydroformylation of 1-octene using Rh/tppts catalysts in the presence of cosolvents such as ethanol to enhance the solubility of the olefin in the aqueous phase and with addition of buffers (Na2C03/NaHC03) to eliminate side reactions such as the formation of acetals.31,365,366 Similarly, addition of ethanol improved the yields in the hydroformylation of 1-octene catalysed by Rh2(p-S-tBu)2(CO)2(tppts)2 species in an aqueous/organic two phase system.367 However, the high selectivity to linear aldehyde observed for neat olefin in the biphasic system (97%) decreased (to 83%) in the presence of the cosolvent.367... 

The aqueous-organic two-phase system was successfully applied to perform hydrocarboxylation.300 Palladium complexes of trisulfonated triphenylphosphine ligands were shown to exhibit high activity.301-303 The application of cosolvents and modified cyclodextrins allow to eliminate solubility problems associated with the transformation of higher alkenes.304... 

From a global assessment of these results, it seems inescapable to conclude that mean-field behavior does not remain valid asymptotically close to the critical point. Rather, ionic systems seem to show Ising-to-mean-field crossover. Such a crossover has been a recurring result observed near liquid-liquid consolute points in Coulombic electrolyte solutions, in ternary aqueous electrolyte solutions containing an organic cosolvent, and in binary aqueous solutions of NaCl near the liquid-vapor critical line. 

One complication that can arise when using Fremy s salt is that the substrate may be insoluble in the aqueous reaction medium, despite the use of organic cosolvents. Olson et al introduced an organic-soluble version of Fremy s salt in their synthesis of a-tocopherol. Hexahydrofamesolacetone (13) was transformed to the phenol (14), which was oxidized in nearly quantitative yield to the tocopheryl quinone (15) using a mixture of Fremy s salt and tricaprylylmethylammonium chloride in a two-phase water/ben-zene solvent system. The oxidizing agent was presumed to be the bis(tricaprylylmethyl)ammonium ni-trodisulfonate. The quinone (15) is a known precursor of a-tocopherol (16 Scheme 4). 

One of the more efficient and versatile methods of increasing solubility and one that does not require modification of the solute is to use an organic cosolvent. The cosolvent reduces the hydrogen bond density of aqueous systems, so that it is less effective in squeezing out non-polar solutes from solution. Cosolvents... 

When a miscible solvent is added to water, the solvent increases the solubility and decreases the sorption of nonionic organic compounds by reducing the net polarity of the solution. The effect of a cosolvent depends on the nature of the solute and the solvent-cosolvent system, but there is usually a log-linear relationship between chemical aqueous solubility and the volumetric fraction of water-miscible solvent (Wood et al, 1990 Bouchard, 2002). 

Lowering the water-activity of the medium [1565] by using water-miscible organic cosolvents such as ethanol or methanol. Alternatively, the reaction can be carried out in a biphasic aqueous-organic system or in a monophasic organic solvent (e.g., ethyl acetate, di-/-propyl, or methyl t-butyl ether) which contains only traces of water to preserve the enz3mie s activity. 

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