Methanol— with weakly solvating solvents

Carbon dioxide, water, ethane, ethylene, propane, ammonia, xenon, nitrous oxide, and fluoroform have been considered useful solvents for SEE. Carbon dioxide has so far been the most widely used as a supercritical solvent because of its convenient critical temperature, 304°K, low cost, chemical stability, nonflammability, and nontoxicity. Its polar character as a solvent is intermediate between a truly nonpolar solvent such as hexane and a weakly polar solvent. Moreover, COj also has a large molecular quadrupole. Therefore, it has some limited affinity with polar solutes. To improve its affinity, additional species are often introduced into the solvent as modifiers. For instance, methanol increases C02 s polarity, aliphatic hydrocarbons decrease it, toluene imparts aromaticity, R-2-butanol adds chirality, and tributyl phosphate enhances the solvation of metal complexes. 

In packed column SFC, polar solutes such as amines and carboxylic acids often have too much retention or elute with poor peak shapes when neat carbon dioxide is used as a mobile phase [28, 92]. This is mainly due to the weak solvent strength of neat carbon dioxide compared to a liquid solvent. The use of modifiers is often necessary to enhance the solvating power of the mobile phase in SFC. Various alcohols such as methanol and isopropanol are commonly used modifiers in SFC, but other solvents such as acetonitrile was also utilized [92]. The concentrations of modifiers are usually less than 50%. The technique in which the concentrations of modifiers are greater than 50% is often called enhanced-fluidity liquid chromatography [93]. 

We suggest the following possible reasons for the absence of anion emission in these experiments First, it is possible for water and methanol to form adducts with CO2 which might inhibit their ability to solvate the proton. This possibility was checked using water as a cosolvent in supercritical ethylene, which will not interact with water data do not indicate formation of an anion therefore solvent/cosolvent adducts are not a plausible explanation. Second, perhaps the anion is being formed but is quenched very efficiently. The anion species would be more susceptible to quenching than the neutral molecule. This possibility could be investigated in principle with fluorescence lifetime studies, but this has not been done. It is entirely possible that the anion emission is so weak as to be hidden underneath the tail of the neutral emission. 

RESS is useful for materials that are soluble in CO2. Unfortunately, CO2, with no dipole moment and very low polarizability, is a very weak solvent and dissolves very few polymers. Cosolvents such as methanol or acetone can be mixed with SCFs to increase the solvating power of SCFs during RESS. In drug delivery applications, RESS has been used to prepare polymeric films, microparticles, nanospheres, liposomes, and porous foams (Figure 1). A... 

Like the alkane solvents discussed previously, CO2 is a poor solvent for nonvolatile hydrophilic molecules. Some enhancement in hydrophile solvation was achieved by addition of cosolvents such as methanol and of complexing agents such as tri- -butyl phosphate [8,54]. Chelating agents have been designed with tails that have highly favorable interactions with CO2, such as fluoroethers and silicones [55]. A much wider range of hydrophilic compounds could be solubilized with surfactants that form reverse micelles and microemulsions in CO2 with polar or aqueous cores. However, extremely few commercial surfactants have tails compatible with the weak van der Waals forces of CO2. This limitation has made the formation of reverse micelles and microemulsions in CO2 more difficult than was the case for the alkane solvents discussed in the previous sections. 

Figure 7 SPE based on reverse-phase chromatography. 1. Solvate the bonded phase with six to ten cartridge holdup volumes of methanol or acetonitrile. Flush the cartridge with six to ten holdup volumes of water or buffer. Do not allow the cartridge to dry out. 2. Load the sample dissolved in a strongly polar solvent. 3. Elute interfering impurities with the strongly polar solvent. 4. Elute weakly held analytes (Analyte 1) of interest with a less polar solvent. 5. Elute more tightly bound analytes (Analyte 2) with progressively more nonpolar solvents.

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