Organized media crystals

All enzymes to be used in organic media have at a previous stage been in an aqueous phase. They are then transferred to the organic medium, and this transfer process involves removal of water. This can be achieved by lyophilization or just drying of the enzyme solution, possibly in the presence of a support material or other additives. Another possibility is to dilute the aqueous enzyme solution with a water-miscible organic solvent which dissolves the water and causes the enzyme to precipitate. In one version, the enzyme solution also contains a crystal-forming solute such as an inorganic salt or an amino acid [20]. In this case, crystals are formed and the enzyme covers the crystals. 

While evaporation is used for the concentration and removal of solvents, usually the reaction by-products are not volatile. Similarly, filtration of precipitated or crystallized solids is not likely to be applicable to all the members of a library, and furthermore the automation of these processes is not straightforward an interesting example of general precipitation of library members from an organic medium due to the presence of a basic ionizable group has been recently reported by Perrier and Labelle (87). Extraction procedures possess the desired separation properties and have been used for the purification of several solution-phase libraries we will cover this subject in more depth in this section. An excellent review (88) has recently been published in which the interested reader will find a description of available strategies for separation and purification of single compounds and arrays. 

The reaction mixture is diluted with 250 ml of water, the mixture is transferred to a 2 liter flask using methanol as a wash liquid, and the organic solvents are distilled at 20-25 mm using a rotary vacuum evaporator. The product separates as a solid and distillation is continued until most of the residual toluene has been removed. The solid is collected on a 90 cm, medium porosity, fritted glass Buchner funnel and washed well with cold water. After the material has been sucked dry, it is covered with a little cold methanol, the mixture is stirred to break up lumps, and the slurry is kept for 5 min. The vacuum is reapplied, the solid is rinsed with a little methanol followed by ether, and the material is air-dried to give 9.1 g (85%), mp 207-213° after sintering at ca. 198°. Reported mp 212-213°. The crude material contains 1.0-1.5% of unreduced starting material as shown by the UV spectrum. Further purification may be effected by crystallization from methanol. 

In almost all theoretical studies of AGf , it is postulated or tacitly understood that when an ion is transferred across the 0/W interface, it strips off solvated molecules completely, and hence the crystal ionic radius is usually employed for the calculation of AGfr°. Although Abraham and Liszi [17], in considering the transfer between mutually saturated solvents, were aware of the effects of hydration of ions in organic solvents in which water is quite soluble (e.g., 1-octanol, 1-pentanol, and methylisobutyl ketone), they concluded that in solvents such as NB andl,2-DCE, the solubility of water is rather small and most ions in the water-saturated solvent exist as unhydrated entities. However, even a water-immiscible organic solvent such as NB dissolves a considerable amount of water (e.g., ca. 170mM H2O in NB). In such a medium, hydrophilic ions such as Li, Na, Ca, Ba, CH, and Br are selectively solvated by water. This phenomenon has become apparent since at least 1968 by solvent extraction studies with the Karl-Fischer method [35 5]. Rais et al. [35] and Iwachido and coworkers [36-39] determined hydration numbers, i.e., the number of coextracted water molecules, for alkali and alkaline earth metal... 

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