Characterization, structure, and stability of channel -type solvates and their isomorphic desolvates
Abstract
Certain channel-type solvates retain their crystal packing arrangements when desolvated. This is indicated by the minimal change in their X-ray powder diffraction (XRPD) patterns during desolvation. The desolvated crystals are called isomorphic desolvates because of the similarity of their molecular packing with those of their solvates. The structures of these solvates are characterized by tunnels and cavities which are occupied by solvent molecules. When the solvent molecules leave the lattice, these tunnels are left empty and become accessible to small molecules. The oxygen reactivity of some such solvates is believed to be associated with solvent loss. When the crystals are desolvated, oxygen molecules are able to diffuse into the lattice through the vacated tunnels and react with the host molecules. This study was carried out to confirm the hypothesis that desolvation when not accompanied by a significant change in the crystal packing arrangement can increase oxidation. The models used in this study were thiamine hydrochloride (THCl) monohydrate and prednisolone t-butyl acetate (PTBA) form V. X-ray powder diffraction and solid-state 13C NMR results indicated, and crystal-structure determination confirmed, that these two hydrates can be dehydrated without significantly altering their crystal structures. Solid-state 13C and 1H T 1 measurements indicate greater motion for the dehydrated crystals, which is consistent with an increase in free volume. The effect of dehydration on oxygen reactivity was different for the two compounds. Neither the hydrated nor the dehydrated form of THCl was reactive towards oxygen. In the case of PTBA, the observation that the isomorphic dehydrate was significantly more reactive than the hydrate confirmed our hypothesis. Oxygen reactivity was also investigated in relation to ease of desolvation. A solvate was prepared by replacing the water molecules of PTBA V with propylene glycol. The lower oxygen reactivity of the propylene glycolate crystal is consistent with its slower desolvation rate. This finding demonstrates that preventing or slowing down the desolvation of solvates that form isomorphic desolvates can increase their stability towards oxidation.
Degree
Ph.D.
Advisors
Byrn, Purdue University.
Subject Area
Pharmacology
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