Aqueous solubility from molecular size

Positive-Tone Photoresists based on Dissolution Inhibition by Diazonaphthoquinones. The intrinsic limitations of bis-azide—cycHzed mbber resist systems led the semiconductor industry to shift to a class of imaging materials based on diazonaphthoquinone (DNQ) photosensitizers. Both the chemistry and the imaging mechanism of these resists (Fig. 10) differ in fundamental ways from those described thus far (23). The DNQ acts as a dissolution inhibitor for the matrix resin, a low molecular weight condensation product of formaldehyde and cresol isomers known as novolac (24). The phenoHc stmcture renders the novolac polymer weakly acidic, and readily soluble in aqueous alkaline solutions. In admixture with an appropriate DNQ the polymer s dissolution rate is sharply decreased. Photolysis causes the DNQ to undergo a multistep reaction sequence, ultimately forming a base-soluble carboxyHc acid which does not inhibit film dissolution. Immersion of a pattemwise-exposed film of the resist in an aqueous solution of hydroxide ion leads to rapid dissolution of the exposed areas and only very slow dissolution of unexposed regions. In contrast with crosslinking resists, the film solubiHty is controUed by chemical and polarity differences rather than molecular size. 

The significance of phenoxy anions is well recognized in the isolation of kraft and other water-insoluble technical lignins by acid precipitation. The ioniza tion of phenoHc hydroxyl groups coupled with the reduction of molecular size renders native lignin soluble in the aqueous pulping solution, thus enabling its separation from the polysaccharide components of wood. 

Griseofulvin, a BCS class II drug (Fig. 2), is a well-known example whose poor aqueous solubility causes low and erratic oral bioavailability. As shown below, griseofulvin has a hydrophobic molecular structure, and is practically insoluble in water. Its oral absorption is highly variable, ranging from 25% to 100%, depending on the crystal size. Ultramicrosize griseofulvin preparations were shown to have 100% oral absorption (12). 

In a review of the thermodynamics of water, Franks and Reid (1973) showed that the optimum molecular size range for maximum solubility was similar to hydrate stability. Franks and Reid noted, this is not intended to imply that long-lived clathrate structures exist in solution—only that the stabilization of the water structure by the apolar solutes resembles the stabilization of water in a clathrate lattice. Glew (1962) noted that, within experimental error, the heat of solution for ten hydrate formers (including methane, ethane, propane, and hydrogen sulfide) was the same as the heat of hydrate formation from gas and ice, thereby suggesting the coordination of the aqueous solute with surrounding water molecules. 

Operationally, it is common to define HS in terms of the methods used to extract or isolate them from soils, sediments, and natural waters. The classic soil extraction procedure yields three main fractions humic acid [also defined as high-molecular-weight (HMW) or high-molecular-size (HMS) fraction], fulvic acid (FA) [also defined as low-molecular-weight (LMW) or low-molecular-size (LMS) fraction], and humin. These fractions are defined in terms of their solubility in aqueous media as a function of pH or in terms of their extractability from soils or sediments as a function of the pH of the extracting medium. Humic acid is the fraction of HS that is not soluble in water under acidic conditions, but becomes soluble (or extractable) at higher pH values. Fulvic acid is the fraction that is soluble in aqueous media at all pH values. Humin represents the fraction that is not soluble in an aqueous medium (or is not extractable with an aqueous medium) at any pH value. Actually, humin consists of an aggregate of humic and nonhumic materials (Rice and Mac-... 

In contrast, Yazaki and Hillis 29) obtained a viscosity of 8,500 mPa-s for a 45% solution of the aqueous extract from Pinus radiata bark. This is almost an order of magnitude higher than that expected on the basis of the procyanidin polymer results. Viscosities of the methanol-soluble portion and the ultrafiltered portions of this extract were 500 and 90 mPa-s, respectively. The former value is about that expected for a proanthocyanidin polymer, but the latter indicates that most of the polymer has been excluded by the filter, and it further implies that molecular sizes of proanthocyanidins based on ultrafiltration measurements are often misleading. 

Physicochemcial properties, such as aqueous solubility, partition coefficient and molecular size, drug stability, and protein binding, are those that can be determined from in vitro experiments. 

Kerr and Severson have superimposed selective precipitation on aqueous extraction technique, by treating the soluble extract with butyl alcohol. This gives an A-fraction (designated by Kerr as crystalline amylose ) of exceptionally high iodine adsorption, but in yields amounting to only 5-6% of the starch. The products from corn and tapioca starches analyze 20.5% and 20.7% iodine adsorption respectively, as compared with a maximum value of 19.0% after four recrystallizations of the Pentasol-precipitated A-fraction from corn starch. This suggests that the A-fraction may be somewhat diversified in molecular size, and that aqueous extraction preferentially dissolves the shorter linear chains. It is not to be expected that all the molecules of a natural high polymer should be of uniform size. 

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