Steric Perturbation to a Channel Hydrate: The Limits of Isomorphism

Abstract

Thymine hydrate (TH) is a classic hydrate system in which water molecules are highly confined in linear one-dimensional channels. Here, we describe our efforts to tune the channel volume by preparing isomorphous mixed crystals with increasing concentrations of uracil (Ur) and 5-ethyluracil (EUr), molecular analogues with slightly smaller and larger volumes, respectively. Solutions with up to 20 mol % Ur successfully yielded isomorphous mixed crystals of TH-Ur x in phase-pure form, though analysis of the mixed crystal compositions indicated that only ∼46% of the Ur available in the initial growth solution was proportionately included in the host lattice. The thermal stability of the mixed TH-Ur x material was significantly altered, with a greater fraction of water loss occurring at low temperature compared to the pure hydrate phase. Isomorphous mixed crystals with EUr substitutions, TH-EUr x , were successfully prepared from solutions with 5–10 mol % EUr, although the fraction of EUr included was much lower (∼13–36%) than Ur. As the concentration of EUr in the growth solution increased to 15–20 mol %, an unexpected mixed composition anhydrate emerged as the dominant crystallization product. Although packing fraction estimates suggested that higher EUr substitution levels in the hydrate were theoretically possible, the formation of the mixed anhydrate presented a more favorable route to a dense material phase.

The First Cocrystallization of Milrinone with Nutraceuticals: The Adjusting Effects of Hydrophilicity/Hydrophobicity in Cavities on the In Vitro/In Vivo Properties of the Cocrystals

“…Thereupon, a two-dimensional layer parallel to plane (1 0 1̅) is constructed by the tetramolecular rings arranged aslant with the angle of 33.397(3)°. Finally, along the b axis, there are discontinuous cavities between the layers, and each cavity is filled with discrete water molecules rather than consecutive water channels, , the two nearest, O7 and O7 vii [symmetry code (vii) − x , 1– y , − z ], compose a couple with O ··· O distance of 3.676(2) Å, the couple links to six tetramolecular rings with hydrogen bonds belong to two layers (Figure b). Consequentially, an entire three-dimensional supramolecular hydrogen-bonding network is completed.…”