Supercooled liquid, water solubility

The last state in Fig. 11.1 that has not yet been discussed is the state of the neat liquid compound X. For liquid compounds this is the relevant initial state for solubility, but almost aU drug-Uke compounds are solid at room temperature. In this case the neat liquid is a virtual state of a supercooled liquid which can hardly be accessed experimentally. However, it is an interesting intermediate state because it allows us to split the calculation of solubility into two separate steps, which are conceptually and for some methods computationally easier to handle than the complete step from the crystaUine state of the drug to the liquid state of the drug dissolved in water. In the first step we only have to transfer the compound from its neat crystalline state to its neat liquid state. The free energy of this fusion transfer is usually called AG s (or if considered in the opposite direction). 

As an example of this nonlinear character we may consider two pairs of compounds, naphthalene versus quinoline and indole versus benzimidazole (Fig. 11.5). In both pairs of compounds the second differs from the first by a mutahon of an aromahc -CH group to an aromahc nitrogen, which introduces a strong H-bond acceptor into the molecule. In quinoline, which has no H-bond donor, the acceptor has no favorable interaction partner in the supercooled liquid or crystalline state, while it can make strong H-bonds with the solvent in water. Therefore, log Sw of quinoline is about 2 log units higher [35, 36] than that of naphthalene, i.e. the introduction of the H-bond acceptor strongly increases solubility in this... 

The plot between Henry s law constant and molar volume (Figure 1.7.4) is more scattered. Figure 1.7.5 shows the often-reported inverse relationship between octanol-water partition coefficient and the supercooled liquid solubility. 

FIGURE 1.7.5 Octanol -water partition coefficient versus molar solubility (liquid or supercooled liquid) for mononuclear aromatic hydrocarbons. 

One drawback with NMR is that the liquid signal from water in o/w emulsions has to be subtracted to obtain the true SFC. This can be done by analyzing emulsions and fat blends with no tendency to supercooling and making calibration curves. Another possibility is to measure reference samples without fat and calculate the true SFC by subtracting the signal from the water and water-soluble components9. 

The water solubility of the supercooled liquid exceeds that of the solid for a given chemical above its melting temperature (tffl). An approximate formula for converting from one to the other is (11 ) ... 

Beautiful deep-red crystals. M.p. 18.5 C. The liquid has a tendency to supercool decomposes at 50°C. Insoluble in water, soluble in organic solvents readily oxidized by air. Can be distilled without extensive decomposition only at temperatures below 15 °C. 

Figure 2.13 Correlation of ATow with at 25°C (Table 2.18) using solubility of tbe supercooled liquid for sobds. [Reproduced with permission of tbe authors from C. T. Cbiou and D. W. Scbmedding, Measurement and Interrelation of Octanol-Water Partition Coefficient and Water Solubility of Organic Chemicals in Test Protocols for Environmental Fate Movement of Toxicants, Proceedings of a Symposium, Association of Official Anal3ffical Chemists, 94th Annual Meeting, Arlington, VA, pp. 28-42, 1981.]...

Cary T. Chiou TABLE IV Octanol-Water Partition Coefficients and Liquid and Supercooled Liquid Solubilities of Selected Aromatic Compounds ... 

Fig. 2. Correlation of octanol-water partition coefficient with water solubility for selected aromatic liquids and solids at 25°C log A ow = -0.862 log S +0.710 (r = 0.994, n - 36). The solubilities of solid compounds in the plot are those of their supercooled liquids at 25°C.

FIGURE 6 Phase distribution equilibria involving pure phases with importance for describing environmental phase partitioning. Kaw, air-water partition coefficient Kow, octanol-water partition coefficient Kqa, octanol-air partition coefficient Pl, (supercooled) liquid vapor pressure Cw and Co, saturation solubility in water and octanol, respectively yw and yo, activity coefficient in water and octanol, respectively. 

Colorless gas mold-hke pungent odor melting point 6.45°C sublimes at 4.77°C supercools to a colorless liquid that boils at 4.5°C liquid density 2.8g/mL at 6°C soluble in water. 

White orthorhombic crystals in pure and anhydrous state or a clear, syrupy liquid melts at 42.35°C hygroscopic can be supercooled into a glass-like solid crystallizes to hemihydrate, H3PO4 I/2H2O on prolonged cooling of 88% solution hemihydrate melts at 29.32°C and loses water at 150°C density 1.834 g/cm3 at 18°C density of commercial H3PO4 (85%) 1.685 g/mL at 25°C pH of 0. IN aqueous solution 1.5 extremely soluble in water, 548 g/lOOmL at room temperature soluble in alcohol. 

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