Date of Award
Doctor of Philosophy in Pharmaceutical Sciences
The effect of varying solvent systems on the solubilities of glycine, L-alanine, L-valine, L-phenylalanine, and DL-aminooctanoic acid at z50 C. was studied. The entire concentration spectrum from pure water to pure semipolar solvent was used for each of. the solvent systems of methanol-water, ethanol-water, n-propanol water, isopropanol-water, and tertiary butanol-water. Further, the effect of pH variation on the solubilities of the amino acids in each of the solvent systems was studied. Aliquots were withdrawn from each solvent system studied and analyzed gravimetrically to determine the resultant solubility. It was found that the solubility behavior of those amino acids studied was a function of the constant effect of the α-amino carboxylic acid portion of the molecule and the independent interactions of the remaining neutral portion of the molecule. Maximum solubility was found in pure water with a reduction to low solubility in the semipolar solvents in the order of a second degree polynomial equation. To each percent strength of the hydroalcoholic solvent systems, the ratio of water to alcoholic molecules per amino acid molecule remains constant. This would indicate that the lengthening of the nonpolar portion of the chain from the hydrogen of glycine to the methyl phenyl of L-phenylalanine 'does not affect the orientation of the water to alcohol molecules in the solvent system. Each of the amino acids studied demonstrated an ability to differentiate between the hydroalcoholic solvents used. The quantitative order of solubility in the solvent systems used varied for each amino acid, but similar solubility profiles could be seen for the entire solvent series. Variation of pH in pure aqueous solvent systems produced an isoelectric band of invariant solubility with a distinct increase in solubility above and below this band. The increase in total solubility of the amino acids· is directly proportional to the number of moles of acid or base added. As the nonpolar portion of the amino acid molecule increased, the total resultant solubility per mole of acid or base added also increased.
In an aquea is system, the total solubility is equal to the sum of the original zwitterion solubility plus the solubility of the salt that was found. For those amino acids studied, only single salts were formed. In the hydroalcoholic solvent systems, variation of pH produced minimum solubility at the isoelectric point with no distinct isoelectric band seen. As the percent alcohol increased in those solvent systems studied, similar increments of acid or base added to the system produced a proportionally greater increase in the magnitude of total solubility of the amino acid. This might be attributed to an increase in the importance of the charge species as the polarity of the solvent system decreased as well as the increased affinity of the amino acid for the Na+ or Cl- ion present.
Needham, Thomas E., "The Solubility of Amino Acids in Various Solvent Systems" (1970). Open Access Dissertations. Paper 159.