Cosolvent effect

T. H. M. Noij, M. E. Margo and M. E. van der Kooi, Automated analysis of polar pesticides in water by on-line solid phase extr action and gas cliromatography using the cosolvent effect , 7. High Resolut. Chromatogr. 18 535-539 (1995). 

Density functional theory study of aqueous-phase rate acceleration and endo/exo selectivity of the butadiene and acrolein Diels-Alder reaction72 shows that approximately 50% of the rate acceleration and endo/exo selectivity is attributed to hydrogen bonding and the remainder to bulk-phase effects, including enforced hydrophobic interactions and cosolvent effects. This appears to be supported by the experimental results of Engberts where a pseudothermodynamic analysis of the rate acceleration in water relative to 1-propanol and 1-propanol-water mixtures indicates that hydrogen-bond stabilization of the polarized activated complex and the decrease of the hydrophobic surface area of the reactants during the activation process are the two main causes of the rate enhancement in water.13... 

The most soluble gasoline compound is methyl tertiary-butyl ether (MTBE) (43,000 mg/L). In addition, MTBE in solution has a cosolvent effect, causing some of the other compounds in gasoline to solubilize at higher concentrations than they normally would in clean water. 

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

Smith, P. E., Computer simulation of cosolvent effects on hydrophobic hydration, J. Phys. Chem. B 1999,103, 525-534... 

Nzengung VA, Voudrias EA, Nkedi-Kizza P, Wampler JM, Weaver CE (1996) Organic cosolvent effects on sorption equilibrium of hydrophobic chemicals by organoclays. Environ Sci Technol 30 89-96... 

The above observations provide a clear demonstration that cosolvents in selected ranges of concentration create reversible perturbations of protein similar to those induced by other modifiers. The reversibility of the cosolvent effect is a prerequisite to cosolvent use and will depend on the concentration of cosolvent, which in turn will vary markedly with the type of solvent used. For instance, polyols can be used at concentrations up to 8 Af while methanol at 3 M causes the appearance of a new absorption band (410 nm) and, after further increases in concentration, an irreversible conversion of cytochrome P-450 into P-420. Other aliphatic alcohols cause denaturation at much lower concentrations. 

As a matter of fact, cosolvents such as primary alcohols, polyols, di-methylformamide and dimethyl sulfoxide are now almost routinely used to perturb the overall reactions and elementary equilibria or rate processes of the highly organized systems carrying out DNA, RNA, and protein synthesis. However, in spite of the fact that such systems respond well and in a reversible way to these perturbations, cosolvent effects remain relatively poor probes of reaction mechanisms (Hamel, 1972 Voigt et al., 1974 Ballesta and Vasquez, 1973 Crepin et ai, 1975 Nakanishi et al., 1974 Brody and Leautey, 1973). The most common result reported upon addition of increasing amounts of cosolvents is a bell-shaped curve equilibria and rate processes are first stimulated and... 

While it is tempting to explain regulatory and cosolvent effects on the basis of conformational changes favorable or unfavorable to enzyme activity, it is much more difficult to demonstrate the actual involvement, amount, and structural details of such changes. Experimental evidence consists in most cases of bits and pieces provided by techniques such as absorption and fluorescence spectroscopy, circular dichroism, and magnetic circular dichroism. These tools work in solution (and, when desired, at subzero temperatures) to investigate not simply empty enzymes but enzyme—substrate intermediates. However, even with this information, the conformational basis of enzyme activity remains more postulated than demonstrated at the ball and stick level, and in spite of data about the number and sequence of intermediates, definition of their approximate nature, rate constants, and identification of the types of catalysis involved, full explanation of any particular reaction cannot be given and rests on speculative hypothesis. 

Table 6.2 presents data showing the effect of various CMOS on the activity coefficient or mole fraction solubility of naphthalene, for two different solvent/water ratios. To examine the cosolvent effect, Schwarzenbach et al. (2003) compare the Hildebrand solubility parameter (defined as the square root of the ratio of the enthalpy of vaporization and the molar volume of the liquid), which is a measure of the cohesive forces of the molecule in pure solvent. 

Current work with supercritical fluids can also illustrate the importance of cosolvents. Cosolvent effects in supercritical fluids can be considerable for systems where the cosolvent interacts strongly with the solute. A correlation suggests that both physical and chemical forces are important in the solvation process in polar cosolvent supercritical CO2 mixtures. The model coupled with the correlation represents a step toward predicting solubilities in cosolvent-modified supercritical fluids using nonthermody-namic data. This method of modeling cosolvent effects allows a more intuitive interpretation of the data than either a purely physical equation of state or ideal chemical theory can provide (Ting et al., 1993). 

We conclude this section with some brief comments on the cosolvent effects of partially miscible organic solvents (PMOSs). These solvents include very polar liquids such as w-butanol, w-butanone, w-pentanol, or o-cresol, but also nonpolar organic compounds such as benzene, toluene, or halogenated methanes, ethanes, and ethenes. For the polar PMOS, a similar effect as for the CMOS can be observed that is, these solvents decrease the activity coefficient of an organic solute when added to pure water or to a CMOS/water mixture (Pinal et al., 1990 Pinal et al., 1991 Li and Andren, 1994). For the less polar PMOS there is not enough data available to draw any general conclusions. 

Bouchard, D. C., Organic cosolvent effects on the sorption and transport of neutral organic chemicals , Chemosphere, 36, 1883-1892 (1998). 

Nzengung, V. A., E. A. Voudrias, and P. Nkedi-Kizza, Organic cosolvent effects on sorption equilibrium of hydrophobic organic chemicals by organoclays , Environ. Sci. Technol., 30, 89-96 (1996). 

Because of the difficulties mentioned above, little use has been made of cosolvent effects in the deduction of mechanism. 

In this work we investigate such interactions by fluorescence spectroscopy. Probe molecules such as 2-naphthol and its 5-cyano-derivative are effective chromophores for studying acid/base interactions since both are relatively strong photo-acids. In addition, 2-naphthol is a common solute for which SCF solubility and physical property data exist. Ultimately, spectroscopic information will be used to develop a clearer picture of the specific interactions which induce large cosolvent effects on solubility in SCF solutions. 

Cosolvent effects on SCF solution behavior allow the tailoring of solvents for extractions and separations. The strong interactions in these systems currently defy prediction by popular computational methods. Only by understanding these interactions at a molecular level will we be able to guide the development of phase equilibria models successfully. One way of exploring the molecular level interactions is with spectroscopy of various kinds and we have demonstrated here an attempt to look at the cosolvent/solute interaction. 

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. 

In this chapter, the uses of cosolvents are discussed with some speciLc limitations. The discussion is limited to the cosolvent effects on solubility and stability, their use in parenteral products. For information on the use of cosolvents in other dosage forms such as soft gelatin capsules, the reader is referred to the speciLc chapter in this book on the topic. 

Tarantino, R., Bishop, E., Chen, F.-C., Iqbal, K., and Malick, AW Methyl-2-pyrrolidone as a cosolvent relationship of cosolvent effect with solute polarity and the presence of proton-donating groups on model drug compoundspharm. Sci., 83,1213-1216, 1994. 

Bouchard, D. C. (2002). Cosolvent effects on sorption isotherm linearity. J. Contam. Hydrol. 56(3 1), 159-174. 

Summary The classical treatment of the physicochemical behavior of polymers is presented in such a way that the chapter will meet the requirements of a beginner in the study of polymeric systems in solution. This chapter is an introduction to the classical conformational and thermodynamic analysis of polymeric solutions where the different theories that describe these behaviors of polymers are analyzed. Owing to the importance of the basic knowledge of the solution properties of polymers, the description of the conformational and thermodynamic behavior of polymers is presented in a classical way. The basic concepts like theta condition, excluded volume, good and poor solvents, critical phenomena, concentration regime, cosolvent effect of polymers in binary solvents, preferential adsorption are analyzed in an intelligible way. The thermodynamic theory of association equilibria which is capable to describe quantitatively the preferential adsorption of polymers by polar binary solvents is also analyzed. 

Keywords Solution properties Conformational analysis Theta condition Excluded volume Good and poor solvent Thermodynamic theories Preferential adsorption Cosolvent effect... 

Polymers in Binary Solvents. Cosolvency Effect Preferential Adsorption Phenomena... 

In general, to explain the observed cosolvent effects, the preferential adsorption phenomena have been invoked. Flowever few topics in the physical chemistry of polymers have evoked so many theories but so little consensus as preferential adsorption. When a polymer is dissolved in a binary solvent mixture, usually one of the solvents preferentially solvates the polymer. This solvent will then be found in a greater proportion in the proximities of the macromolecule with respect to the bulk solution composition. This variation of the solvent composition can cause interesting phenomena such as cosolvency as was discussed before, [11, 91, 92] non - cosolvency [93, 94], and some times variation of the unperturbed polymer dimensions [95,96]... 

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